Methanol → HCID 86681007, compound

HRID 1847969Notes

Reaction equation

HRID 1847969 reaction equation
[NH:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[CH:3]=[CH:2]1.[OH-].[K+].[OH:12][C@@H:13]1[CH2:18][CH2:17][CH2:16][CH2:15][C@H:14]1[NH:19][C:20]1[S:21][C:22]2[CH:28]=[C:27]([CH:29]=[O:30])[CH:26]=[CH:25][C:23]=2[N:24]=1.[CH3:31]O>CCOC(C)=O>[CH3:31][O:30][CH:29]([C:3]1[C:4]2[C:5](=[N:6][CH:7]=[CH:8][CH:9]=2)[NH:1][CH:2]=1)[C:27]1[CH:26]=[CH:25][C:23]2[N:24]=[C:20]([NH:19][C@@H:14]3[CH2:15][CH2:16][CH2:17][CH2:18][C@H:13]3[OH:12])[S:21][C:22]=2[CH:28]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 92221H-Pyrrolo(2,3-b)pyridineHCID 14797Potassium HydroxideHCID 86681006HCID 86681006, compound

Product 1

HCID 86681007HCID 86681007, compoundYield 5.4%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1H-pyrrolo[2,3-b]pyridine (205 mg, 1.74 mmol) in MeOH (20 mL) were added potassium hydroxide (162 mg, 2.9 mmol) and 2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]thiazole-6-carbaldehyde from Step 2 of this Example (400 mg, 1.45 mmol) sequentially at rt. The reaction mixture was stirred at rt for 14 d. The resulting mixture was diluted with EtOAc (80 mL) and washed with water, brine. The organic layer was dried over MgSO4, and concentrated under reduced pressure. The crude product was 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 (1R,2R)-2-((6-(methoxy(1H-pyrrolo[2,3-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol as a white solid (32 mg, 5.4%). 1H NMR (300 MHz, CDCl3) δ 9.70 (br s, 1H), 8.26 (dd, J=1.4, 4.8 Hz, 1H), 7.85 (dd, J=1.3, 7.7 Hz, 1H), 7.64 (d, J=1.3 Hz, 1H), 7.44-7.54 (m, 1H), 7.34 (d, J=8.3 Hz, 1H), 6.97-7.11 (m, 2H), 5.64 (br s, 1H), 5.56 (s, 1H), 3.44-3.67 (m, 3H), 3.42 (s, 3H), 2.06-2.27 (m, 2H), 1.65-1.87 (m, 2H), 1.14-1.53 (m, 4H). LCMS (ESI) m/z 409 (M+H)+.

Workup

  1. washwashed with water, brine
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated under reduced pressure
  4. customThe crude product was purified by HPLC
  5. 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-a5415b44f5054c4a881a8fa401c97918
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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