Acetyl chloride → HCID 72709646, compound

HRID 1505695Notes

Reaction equation

HRID 1505695 reaction equation
[C:1](Cl)(=[O:3])[CH3:2].Cl.[CH3:6][N:7]1[CH:11]=[C:10]([C:12]2[CH:13]=[C:14]([C:18]3[N:23]=[CH:22][C:21]([C:24]4[CH:25]=[N:26][N:27]([CH:29]5[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]5)[CH:28]=4)=[CH:20][N:19]=3)[CH:15]=[CH:16][CH:17]=2)[CH:9]=[N:8]1>CN(C=O)C.C(Cl)Cl>[CH3:6][N:7]1[CH:11]=[C:10]([C:12]2[CH:13]=[C:14]([C:18]3[N:19]=[CH:20][C:21]([C:24]4[CH:25]=[N:26][N:27]([CH:29]5[CH2:34][CH2:33][N:32]([C:1](=[O:3])[CH3:2])[CH2:31][CH2:30]5)[CH:28]=4)=[CH:22][N:23]=3)[CH:15]=[CH:16][CH:17]=2)[CH:9]=[N:8]1

Participants

5

Reactant 2

HCID 6367Acetyl chlorideHCID 89924162HCID 89924162, compound

Product 1

HCID 72709646HCID 72709646, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Acetyl chloride (222 μl; 3.1 mmol; 2.0 eq.) was added to a solution of 2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyrimidine hydrochloride (example 1, 655 mg; 1.55 mmol; 1.0 eq.) and TEA (503 μl; 3.88 mmol; 2.5 eq.) in dry DMF (12 mL) and the reaction mixture was stirred at RT and under nitrogen for 2 h. The reaction mixture was diluted with DCM and washed with water. Organic phase was washed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by flash chromatography on silica (DCM: MeOH, gradient 100:0 to 80:20) afforded the title compound as a white solid (370 mg, 56%). 1H NMR (300 MHz, DMSO-d6) δ 9.16 (s, 2H), 8.58-8.50 (m, 2H), 8.26 (s, 1H), 8.21 (dt, J=8.0, 1.5 Hz, 1H), 8.15 (s, 1H), 7.92 (s, 1H), 7.71 (dt, J=8.0, 1.5 Hz, 1H), 7.51 (t, J=8.0 Hz, 1H), 4.58-4.43 (m, 2H), 4.01-3.83 (m, 4H), 3.29-3.17 (m, 1H), 2.74 (dd, J=14.1, 9.2 Hz, 1H), 2.19-2.02 (m, 5H), 1.98-1.69 (m, 2H). HPLC (Condition A): Rt 2.90 min (purity 98.0%). MS (ESI+): 428.36.

Workup

  1. washwashed with water
  2. washOrganic phase was washed with brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by flash chromatography on silica (DCM: MeOH, gradient 100:0 to 80:20)

Sources & evidence

ORD record
ord-cf2b3b017b744a94a647c093e9f902f9
Source dataset
uspto-grants-2015_12
Patent number
US09216991B2

Reaction notes

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