(2,3-Difluorophenyl)boronic acid → (6bR,10aS)-5-(2,3-difluorophenyl)-1,2,6b,7,8,9,10,10a-octahydropyrido[4,3-b][1,4]thiazino[2,3,4-hi]indole

HRID 51031Notes

Reaction equation

HRID 51031 reaction equation
BrC1C=C2C3=C(SCCN3[C@H]3CCN(C(OC(C)(C)C)=O)C[C@@H]23)C=1.FC1C(F)=CC=CC=1B(O)O.[F:36][C:37]1[C:42]([F:43])=[CH:41][CH:40]=[CH:39][C:38]=1[C:44]1[CH:45]=[C:46]2[C:50]3=[C:51]([S:53][CH2:54][CH:55]([C:56]([O:58][C:59]([CH3:62])([CH3:61])[CH3:60])=[O:57])[N:49]3[C@H:48]3[CH2:63][CH2:64][N:65]=[CH:66][C@H:47]23)[CH:52]=1>>[F:36][C:37]1[C:42]([F:43])=[CH:41][CH:40]=[CH:39][C:38]=1[C:44]1[CH:45]=[C:46]2[C:50]3=[C:51]([S:53][CH2:54][CH:55]([C:56]([O:58][C:59]([CH3:62])([CH3:61])[CH3:60])=[O:57])[N:49]3[C@H:48]3[CH2:63][CH2:64][N:65]=[CH:66][C@H:47]23)[CH:52]=1.[F:36][C:37]1[C:42]([F:43])=[CH:41][CH:40]=[CH:39][C:38]=1[C:44]1[CH:45]=[C:46]2[C:50]3=[C:51]([S:53][CH2:54][CH2:55][N:49]3[C@H:48]3[CH2:63][CH2:64][NH:65][CH2:66][C@@H:47]23)[CH:52]=1

Participants

5

Reactant 3

HCID 2734333(2,3-Difluorophenyl)boronic acidHCID 21302667tert-butyl(6bR,10aS)-5-bromo-1,2,6b,9,10,10a-hexahydropyrido[4,3-b][1,4]thiazino[2,3,4-hi]indole-8(7H)-carboxylateHCID 86759405Tert-butyl(6bR,10aS)-5-(2,3-difluorophenyl)-1,2,6b,9,10,10a-hexahydropyrido[4,3-b][1,4]thiazino[2,3,4-hi]indole carboxylate

Product 2

HCID 69515062(6bR,10aS)-5-(2,3-difluorophenyl)-1,2,6b,7,8,9,10,10a-octahydropyrido[4,3-b][1,4]thiazino[2,3,4-hi]indoleYield 96%HCID 86759405Tert-butyl(6bR,10aS)-5-(2,3-difluorophenyl)-1,2,6b,9,10,10a-hexahydropyrido[4,3-b][1,4]thiazino[2,3,4-hi]indole carboxylateYield 45%

Procedure

Tert-butyl(6bR,10aS)-5-(2,3-difluorophenyl)-1,2,6b,9,10,10a-hexahydropyrido[4,3-b][1,4]thiazino[2,3,4-hi]indole carboxylate (50 mg, 45%) was prepared by the method of Example 443 Step A as a yellow oil from tert-butyl(6bR,10aS)-5-bromo-1,2,6b,9,10,10a-hexahydropyrido[4,3-b][1,4]thiazino[2,3,4-hi]indole-8(7H)-carboxylate (100 mg, 0.25 mmol) and 2,3-difluorophenylboronic acid (80 mg, 0.50 mmol). The title compound (22 mg, 96%) was prepared by the method of Example 443 Step B as a yellow oil from tert-butyl(6bR,10aS)-5-(2,3-difluorophenyl)-1,2,6b,9,10,10a-hexahydropyrido[4,3-b][1,4]thiazino[2,3,4-hi]indole carboxylate (30 mg, 0.067 mmol). 1H NMR (CDCl3, 300 MHz) δ1.91-2.05 (m, 2H), 2.60-2.80 (m, 1H), 2.81-3.02 (m, 2H), 3.03-3.18 (m, 2H), 3.20-3.38 (m, 2H), 3.39-3.63 (m, 4H), 6.97 (dd, J=22.4, 2.2 Hz, 1H), 7.02-7.14 (m, 4H) ppm.

Sources & evidence

ORD record
ord-e179b7e4f99746429e4dfed2d23e39e5
Source dataset
uspto-grants-2004_03
Patent number
US06713471B1

Reaction notes

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