Pyridine → (R)-2-((6-((3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanone oxime

HRID 1848033Notes

Reaction equation

[N:1]1[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[N:3]([CH2:10][C:11]2[CH:27]=[CH:26][C:14]3[N:15]=[C:16]([NH:18][C@@H:19]4[CH2:24][CH2:23][CH2:22][CH2:21][C:20]4=O)[S:17][C:13]=3[CH:12]=2)[CH:2]=1.N1C=CC=CC=1.[NH2:34][OH:35].Cl>CCO>[N:1]1[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[N:3]([CH2:10][C:11]2[CH:27]=[CH:26][C:14]3[N:15]=[C:16]([NH:18][C@@H:19]4[CH2:24][CH2:23][CH2:22][CH2:21][C:20]4=[N:34][OH:35])[S:17][C:13]=3[CH:12]=2)[CH:2]=1

Participants

Conditions

Temperature: 88 °C

Procedure

(R)-2-((6-((3H-Imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanone from Example 54 (70 mg, 0.19 mmol) was stirred in EtOH. Pyridine (100 μL, excess) and NH2OH.HCl (100 mg, excess) were added and the resulting mixture was heated at 88° C. for 1 h. LCMS showed that the reaction was complete. The mixture was then cooled to rt and purified by HPLC using a mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C-18 column as the stationary phase to afford (R)-2-((6-((3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanone oxime (53 mg, 73%) as a white powder. 1H NMR (300 MHz, DMSO-d6) δ 10.57 (s, 1H), 8.60 (s, 1H), 8.38 (d, J=4.0 Hz, 1H), 8.13-8.27 (m, 1H), 8.09 (dd, J=0.8, 7.9 Hz, 1H), 7.58-7.76 (m, 1H), 7.10-7.39 (m, 3H), 5.49 (s, 2H), 4.33-4.77 (m, 1H), 2.69-2.95 (m, 1H), 1.92-2.38 (m, 2H), 1.26-1.86 (m, 5H). LCMS (ESI) m/z 393 (M+H)+.

Workup

temperatureThe mixture was then cooled to rt
custompurified by HPLC
additiona mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C-18 column as the stationary phase

Sources & evidence

ORD record: ord-c96ce33f6f7c49b699f23175f7d0aecd
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08952058B2

Reaction notes

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