Pyridine → HCID 136359793, compound

HRID 1848236Notes

Reaction equation

HRID 1848236 reaction equation
[OH:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][C:9]1[S:10][C:11]2[CH:17]=[C:16]([CH2:18][C:19]3[N:23]4[CH:24]=[CH:25][C:26]([C:28](=O)[CH3:29])=[CH:27][C:22]4=[N:21][CH:20]=3)[CH:15]=[CH:14][C:12]=2[N:13]=1.Cl.[NH2:32][OH:33].N1C=CC=CC=1>CCO>[OH:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][C:9]1[S:10][C:11]2[CH:17]=[C:16]([CH2:18][C:19]3[N:23]4[CH:24]=[CH:25][C:26]([C:28](=[N:32][OH:33])[CH3:29])=[CH:27][C:22]4=[N:21][CH:20]=3)[CH:15]=[CH:14][C:12]=2[N:13]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 443297Hydroxyamine hydrochlorideHCID 86681207HCID 86681207, compound

Product 1

HCID 136359793HCID 136359793, compoundYield 61%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred solution of 1-(3-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]thiazol-6-yl)methyl)imidazo[1,2-a]pyridin-7-yl)ethanone (40 mg, 0.095 mmol) from Example 200 in EtOH (2 mL) at rt were added hydroxylamine hydrochloride (120 mg, excess) and pyridine (200 μL, excess). The mixture was heated at 90° C. for 1 h, and then cooled to rt. Purification by reverse-phase HPLC using a mixture of water (5% CH3CN, 0.05% HCOOH), CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C18 column as the stationary phase afforded 1-(3-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]thiazol-6-yl)methyl)imidazo[1,2-a]pyridin-7-yl)ethanone oxime (23 mg, 61%) as yellow powder. 1H NMR (500 MHz, DMSO-d6) δ 11.46 (br s, 1H), 8.13 (d, J=7.4 Hz, 1H), 7.90 (d, J=7.4 Hz, 1H), 7.72 (s, 1H), 7.51 (s, 1H), 7.45 (s, 1H), 7.08 (d, J=8.4 Hz, 1H), 6.44-6.58 (m, 1H), 5.89 (s, 1H), 4.78 (d, J=2.5 Hz, 1H), 4.29 (s, 2H), 3.50 (br s, 1H), 2.18 (s, 3H), 2.04 (d, J=12.3 Hz, 1H), 1.87 (d, J=10.8 Hz, 1H), 1.56-1.67 (m, 2H), 1.15-1.32 (m, 4H). LCMS (ESI) m/z 436 (M+H)+.

Workup

  1. temperaturecooled to rt
  2. customPurification by reverse-phase
  3. additiona mixture of water (5% CH3CN, 0.05% HCOOH), CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C18 column as the stationary phase

Sources & evidence

ORD record
ord-f366f8c5510644e39e0e6e2272a20d3a
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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