Claims for Patent: 6,020,487

Summary for Patent: 6,020,487

Title:	Intermediates and process for preparing olanzapine
Abstract:	The present invention provides a process for preparing olanzapine and intermediates therefor.
Inventor(s):	Charles Arthur Bunnell, Samuel Dean Larsen, John Richard Nichols, Susan Marie Reutzel, Gregory Alan Stephenson
Assignee:	Eli Lilly and Co
Application Number:	US08/935,884
Patent Claims:	1. An olanzapine dihydrate selected from Dihydrate B and Dihydrate E. 2. A dihydrate of claim 1 which is crystalline Dihydrate B and which has a typical X-ray powder diffraction pattern with the following interplanar spacings (d) in Angstroms: ______________________________________ ______________________________________ 9.9045 6.9985 6.7630 6.4079 6.1548 6.0611 5.8933 5.6987 5.4395 5.1983 5.0843 4.9478 4.7941 4.6960 4.5272 4.4351 4.3474 4.2657 4.1954 4.0555 3.9903 3.9244 3.8561 3.8137 3.7671 3.6989 3.6527 3.5665 3.4879 3.3911 3.3289 3.2316 3.1982 3.1393 3.0824 2.9899 2.9484 2.9081 2.8551 2.8324 2.7510 2.7323 2.6787 2.6424 2.5937. ______________________________________ 3. A Dihydrate B of claim 2 wherein the diffraction pattern has the following typical relative intensity (I/I1) pattern: ______________________________________ d I/I.sub.1 ______________________________________ 9.9045 100.00 6.9985 0.39 6.7630 0.17 6.4079 0.13 6.1548 0.85 6.0611 0.99 5.8933 0.35 5.6987 0.12 5.4395 1.30 5.1983 0.67 5.0843 0.24 4.9478 0.34 4.7941 6.53 4.6960 1.26 4.5272 2.65 4.4351 2.18 4.3474 1.85 4.2657 0.49 4.1954 0.69 4.0555 0.42 3.9903 0.89 3.9244 1.52 3.8561 0.99 3.8137 1.44 3.7671 0.92 3.6989 1.78 3.6527 O.60 3.5665 0.34 3.4879 1.41 3.3911 0.27 3.3289 0.20 3.2316 0.31 3.1982 0.19 3.1393 0.35 3.0824 0.18 2.9899 0.26 2.9484 0.38 2.9081 0.29 2.8551 0.37 2.8324 0.49 2.7510 0.37 2.7323 0.64 2.6787 0.23 2.6424 0.38 2.5937 0.21 ______________________________________ 4. A Dihydrate B of claim 3 in substantially pure form. 5. A dihydrate of claim 1 which is crystalline Dihydrate E and which has a typical X-ray powder diffraction pattern with the following interplanar spacings (d) in Angstroms: ______________________________________ ______________________________________ 9.8710 9.5514 6.9575 6.1410 6.0644 5.9896 5.8774 4.7721 4.6673 4.5171 4.4193 4.3540 4.2539 4.2369 4.0537 4.0129 3.8555 3.7974 3.6846 3.5541 3.4844 3.4740 3.4637 3.3771 3.1245 2.9403. ______________________________________ 6. A Dihydrate E of claim 5 wherein the diffraction pattern has the following typical relative intensity pattern (I/I1): ______________________________________ d I/I.sub.1 ______________________________________ 9.917 100.00 9.6046 16.75 7.0163 2.44 6.1987 8.78 6.0971 10.62 5.9179 1.73 4.8087 50.14 4.7140 10.24 4.5335 14.20 4.4531 7.80 4.3648 3.04 4.2760 4.50 4.0486 2.76 3.8717 5.09 3.8292 13.39 3.7053 17.24 3.5827 4.82 3.4935 13.22 3.3982 2.01 3.3294 1.30 3.2026 0.98 3.1450 2.66 3.1225 1.63 3.0880 2.11 2.9614 2.49 2.9014 1.03 2.8695 2.06 2.8359 1.63 2.7647 1.95 2.7582 1.68 2.7496 1.84 2.7421 1.03 2.7347 1.36 2.6427 2.01 ______________________________________ 7. A Dihydrate E of claim 6 in substantially pure form. 8. A process for preparing substantially pure Form II olanzapine comprising preparing an olanzapine dihydrate selected from Dihydrate B, Dihydrate D and Dihydrate E and drying it until the Form II is prepared. 9. A process of claim 8 wherein the dihydrate is dried in a vacuum oven at about 40° C. to about 70° C. 10. A process of claim 9 wherein the dihydrate is Dihydrate D. 11. A process of claim 9 wherein the dihydrate is Dihydrate B. 12. A process of claim 9 wherein the dihydrate is Dihydrate E.