Pyridine → HCID 71548898, compound

HRID 1848082Notes

Reaction equation

HRID 1848082 reaction equation
C([O:4][C@@H:5]1[CH2:10][CH2:9][CH2:8][CH2:7][C@H:6]1[NH:11][C:12]1[S:13][C:14]2[CH:20]=[C:19]([CH2:21][N:22]3[C:26]4=[N:27][CH:28]=[C:29]([CH2:31][NH2:32])[CH:30]=[C:25]4[N:24]=[CH:23]3)[CH:18]=[CH:17][C:15]=2[N:16]=1)(=O)C.N1C=CC=CC=1.[C:39](Cl)([CH3:41])=[O:40]>C(Cl)Cl>[OH:4][C@@H:5]1[CH2:10][CH2:9][CH2:8][CH2:7][C@H:6]1[NH:11][C:12]1[S:13][C:14]2[CH:20]=[C:19]([CH2:21][N:22]3[C:26]4=[N:27][CH:28]=[C:29]([CH2:31][NH:32][C:39](=[O:40])[CH3:41])[CH:30]=[C:25]4[N:24]=[CH:23]3)[CH:18]=[CH:17][C:15]=2[N:16]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 6367Acetyl chlorideHCID 89498430HCID 89498430, compound

Product 1

HCID 71548898HCID 71548898, compoundYield 83.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (1R,2R)-2-((6-((6-(aminomethyl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (50 mg, 0.12 mmol) from Example 91 in DCM (2 mL) were added pyridine (40 μL, 0.48 mmol) and AcCl (27 μL, 0.36 mmol). The resulting mixture was stirred at rt for 3 h before it was concentrated under reduced pressure. The residue was purified by reverse-phase preparative HPLC using a mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C18 column as the stationary phase to afford N-((3-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]thiazol-6-yl)methyl)-3H-imidazo[4,5-b]pyridin-6-yl)methyl)acetamide (45 mg, 82%) as a white powder. 1H NMR (300 MHz, DMSO-d6) δ 8.58 (s, 1H), 8.40 (br s, 1H), 8.31 (s, 1H), 7.84-8.10 (m, 2H), 7.65 (s, 1H), 7.24-7.41 (m, 1H), 7.10-7.24 (m, 1H), 5.47 (s, 2H), 4.37 (d, J=5.5 Hz, 2H), 3.34 (d, J=8.7 Hz, 2H), 1.97-2.16 (m, 1H), 1.89 (br s, 1H), 1.86 (s, 3H), 1.61 (br s, 2H), 0.99-1.39 (m, 4H). LCMS (ESI) m/z 451 (M+H)+.

Workup

  1. concentrationwas concentrated under reduced pressure
  2. customThe residue was purified by reverse-phase preparative HPLC
  3. additiona mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C18 column as the stationary phase

Sources & evidence

ORD record
ord-97a33ca7c5b04dd49474b7c13cac6476
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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