Potassium Carbonate → 4-(5-{3-[(4-Cyclobutylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-1,4-diazepan-2-one

HRID 1028117Notes

Reaction equation

HRID 1028117 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH:8]2[CH2:11][CH2:10][CH2:9]2)[CH:5]=[CH:4][N:3]=1.[NH2:12][C:13]1[CH:14]=[C:15]([C:20]2[S:24][C:23]([N:25]3[CH2:31][CH2:30][CH2:29][NH:28][C:27](=[O:32])[CH2:26]3)=[N:22][CH:21]=2)[CH:16]=[C:17]([CH3:19])[CH:18]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C(=O)([O-])[O-].[K+].[K+]>C(O)(CC)(C)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:8]1([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:12][C:13]3[CH:14]=[C:15]([C:20]4[S:24][C:23]([N:25]5[CH2:31][CH2:30][CH2:29][NH:28][C:27](=[O:32])[CH2:26]5)=[N:22][CH:21]=4)[CH:16]=[C:17]([CH3:19])[CH:18]=3)[N:7]=2)[CH2:11][CH2:10][CH2:9]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 497584742-Chloro-4-cyclobutylpyrimidineHCID 67236328HCID 67236328, compound2×

Product 1

HCID 672421904-(5-{3-[(4-Cyclobutylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-1,4-diazepan-2-oneYield 74,074.102%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 64052-Methyl-2-butanolSolvent

Conditions

Temperature
90 °C

Procedure

2-Chloro-4-cyclobutylpyrimidine (50 mg, 0.297 mmol), 4-[5-(3-amino-5-methylphenyl)-1,3-thiazol-2-yl]-1,4-diazepan-2-one (Intermediate XX, 90 mg, 0.297 mmol), Pd2(dba)3 (27.2 mg, 0.030 mmol), XPhos (70.7 mg, 0.148 mmol), and potassium carbonate (82 mg, 0.593 mmol) were combined in t-amyl alcohol (0.99 ml). The mixture was purged with argon for 5 minutes, capped, and stirred at 90° C. overnight. The mixture was then cooled to room temperature and loaded directly on the column and was purified by silica gel chromatography (10% methanol/dichloromethane) to provide 98 mg (0.22 mol, 76% yield) of 4-(5-{3-[(4-cyclobutylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-1,4-diazepan-2-one as a tan solid. MS APCI: [M+H]+ m/z 435.2. 1H NMR (600 MHz, d6-DMSO) δ 9.48 (s, 1H), 8.32 (d, J=4.8 Hz, 1H), 7.92 (s, 1H), 7.55 (dd, J=4.8 Hz, 5.4 Hz, 1H), 7.43 (s, 1H), 7.38 (s, 1H), 6.88 (s, 1H), 6.66 (d, J=5.4 Hz, 1H), 4.14 (s, 2H), 3.75 (m, 2H), 3.52 (m, 1H), 3.18 (m, 2H), 2.33-2.23 (m, 4H), 2.24 (s, 3H), 2.02 (m, 1H), 1.88 (m, 1H), 1.76 (m, 2H). rhSYK activity=+++

Workup

  1. customThe mixture was purged with argon for 5 minutes
  2. customcapped
  3. temperatureThe mixture was then cooled to room temperature
  4. customwas purified by silica gel chromatography (10% methanol/dichloromethane)

Sources & evidence

ORD record
ord-c8960659761e4daf8744b0d75c9e2337
Source dataset
uspto-grants-2014_05
Patent number
US08735417B2

Reaction notes

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