Potassium Carbonate → (2 S)-2-[4-(4-{[(1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl]methoxy}-2-methylpyrimidin-5-yl)-1H-pyrazol-1-yl]propan-1-ol

HRID 872058Notes

Reaction equation

HRID 872058 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C@H:9]2[CH2:11][C@@H:10]2[CH2:12][O:13][C:14]2[C:19]([C:20]3[CH:21]=[N:22][NH:23][CH:24]=3)=[CH:18][N:17]=[C:16]([CH3:25])[N:15]=2)=[N:7][CH:8]=1.Cl[C@@H:27]([CH3:30])[CH2:28][OH:29].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C@H:9]2[CH2:11][C@@H:10]2[CH2:12][O:13][C:14]2[C:19]([C:20]3[CH:24]=[N:23][N:22]([C@@H:27]([CH3:30])[CH2:28][OH:29])[CH:21]=3)=[CH:18][N:17]=[C:16]([CH3:25])[N:15]=2)=[N:7][CH:8]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 641045(S)-(+)-2-Chloro-1-propanolHCID 710612104-{[(1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl]methoxy}-2-methyl-5-(1H-pyrazol-4-yl)pyrimidine

Product 1

HCID 117689143(2 S)-2-[4-(4-{[(1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl]methoxy}-2-methylpyrimidin-5-yl)-1H-pyrazol-1-yl]propan-1-ol

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-{[(1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl]methoxy}-2-methyl-5-(1H-pyrazol-4-yl)pyrimidine (NN1) (15 mg, 0.04 mmol) in DMF (0.4 mL) was added and (2S)-2-chloropropan-1-ol (9.0 mg, 0.09 mmol) and potassium carbonate (18.4 mg, 0.13 mmol). The reaction mixture was stirred at ambient temperature for 14 hours. The mixture was filtered and purified by reverse phase chromatography (Waters Sunfire Prep C18 OBD, 5-45% acetonitrile in water with 0.1% TFA modifier) to afford the title compound as a white solid. 1H NMR (500 MHz, DMSO): δ 8.74 (s, 1 H), 8.13 (d, J=11.7 Hz, 2 H), 8.00 (s, 1 H), 7.27 (d, J=7.1 Hz, 2 H), 4.55-4.50 (m, 1 H), 4.37-4.30 (m, 1 H), 3.96 (s, 3 H), 3.78 (s, 3 H), 2.50 (s, 3 H), 2.22 (d, J=7.1 Hz, 1 H), 1.80 (s, 1 H), 1.25-1.16 (m, 2 H), 1.07 (m, 1 H), 1.01 (d, J=5.3 Hz, 3 H); HRMS m/z (M+H) 396.2019 found, 396.2030 required.

Workup

  1. filtrationThe mixture was filtered
  2. custompurified by reverse phase chromatography (Waters Sunfire Prep C18 OBD, 5-45% acetonitrile in water with 0.1% TFA modifier)

Sources & evidence

ORD record
ord-4554157ff9c542119e3c737ff980a63f
Source dataset
uspto-grants-2015_03
Patent number
US08975261B2

Reaction notes

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