Acetyl chloride → HCID 58456172, compound

HRID 410584Notes

Reaction equation

HRID 410584 reaction equation
[NH2:1][C:2]1([C:6]2[S:7][C:8]([C:11]3[CH:12]=[C:13]([NH:18][C:19]4[N:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:21][N:20]=4)[CH:14]=[C:15]([CH3:17])[CH:16]=3)=[CH:9][N:10]=2)[CH2:5][CH2:4][CH2:3]1.CCN(CC)CC.[C:36](Cl)(=[O:38])[CH3:37]>C1COCC1.C(OCC)(=O)C>[CH3:17][C:15]1[CH:16]=[C:11]([C:8]2[S:7][C:6]([C:2]3([NH:1][C:36](=[O:38])[CH3:37])[CH2:3][CH2:4][CH2:5]3)=[N:10][CH:9]=2)[CH:12]=[C:13]([NH:18][C:19]2[N:24]=[C:23]([C:25]([F:27])([F:28])[F:26])[CH:22]=[CH:21][N:20]=2)[CH:14]=1

Participants

6

Reactant 3

HCID 6367Acetyl chloride2×HCID 8471TriethylamineHCID 67257371HCID 67257371, compound

Product 1

HCID 58456172HCID 58456172, compoundYield 92.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-{3-[2-(1-aminocyclobutyl)-1,3-thiazol-5-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amine (Example 61B-1, 75 mg, 0.185 mmol) and Et3N (25.8 μL, 0.185 mmol) in THF (1000 μL), acetyl chloride (13.15 μL, 0.185 mmol) was added. The mixture was stirred at room temperature for 70 minutes. Additional acetyl chloride (6 μL) was added to drive the reaction to completion. The mixture was stirred for 10 additional minutes, then diluted with ethyl acetate, washed with saturated NaHCO3, followed by brine, dried (Na2SO4), filtered and concentrated to afford N-{1-[5-(3-methyl-5-{[4-(trifluoromethyl)-pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclobutyl}acetamide (80.8 mg, 0.171 mmol, 92%). MS ESI: [M+H]+ m/z 480.0. 1H NMR (500 MHz, DMSO-d6) δ 10.25 (s, 1H), 8.93 (s, 1H), 8.83 (d, J=4.9 Hz, 1H), 8.00 (s, 1H), 7.94 (s, 1H), 7.42 (s, 1H), 7.28 (d, J=4.9 Hz, 1H), 7.14 (s, 1H), 3.32-2.60 (m, 2H), 2.43-2.41 (m, 2H), 2.31 (s, 3H), 1.99-1.95 (m, 2H), 1.88 (s, 3H). rhSYK activity=+++

Workup

  1. customthe reaction to completion
  2. stirringThe mixture was stirred for 10 additional minutes
  3. washwashed with saturated NaHCO3
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-3a99e24d0b08452fb589e7caf8b4a634
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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