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

HRID 1028126Notes

Reaction equation

HRID 1028126 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:9]2[S:13][C:12]([N:14]3[CH2:20][CH2:19][CH2:18][NH:17][C:16](=[O:21])[CH2:15]3)=[N:11][CH:10]=2)[CH:5]=[C:6]([CH3:8])[CH:7]=1.Cl[C:23]1[N:28]=[C:27]([CH3:29])[C:26]([Cl:30])=[CH:25][N:24]=1.C(=O)([O-])[O-].[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)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]>[Cl:30][C:26]1[C:27]([CH3:29])=[N:28][C:23]([NH:1][C:2]2[CH:3]=[C:4]([C:9]3[S:13][C:12]([N:14]4[CH2:20][CH2:19][CH2:18][NH:17][C:16](=[O:21])[CH2:15]4)=[N:11][CH:10]=3)[CH:5]=[C:6]([CH3:8])[CH:7]=2)=[N:24][CH:25]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 212786212,5-Dichloro-4-methylpyrimidineHCID 67236328HCID 67236328, compound2×

Product 1

HCID 672402244-(5-{3-[(5-Chloro-4-methylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-1,4-diazepan-2-oneYield 51%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
90 °C

Procedure

A sealed tube was charged with a stir bar, 4-[5-(3-amino-5-methylphenyl)-1,3-thiazol-2-yl]-1,4-diazepan-2-one (Intermediate XX, 75 mg, 0.25 mmol), 2,5-dichloro-4-methylpyrimidine (40 mg, 0.25 mmol), potassium carbonate (69 mg, 0.50 mmol), Pd2(dba)3 (23 mg, 0.025 mmol), and XPhos (59 mg, 0.124 mmol). The tube was evacuated and backfilled with argon three times. Fully degassed t-amyl alcohol (0.83 ml) was added and the tube was sealed and heated at 90° C. for overnight. The resulting slurry was diluted with methanol, absorbed onto 1.5 g of silica, and purified via silica gel chromatography (0-20% methanol in ethyl acetate) to afford 54 mg (0.126 mmol, 51% yield) of 4-(5-{3-[(5-Chloro-4-methylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-1,4-diazepan-2-one as a yellow solid. MS APCI: [M+H]+ m/z 429.1. 1H NMR (500 MHz, dmso) δ 9.73 (s, 1H), 8.42 (s, 1H), 7.74 (s, 1H), 7.59 (t, J=5.0 Hz, 1H), 7.46 (s, 1H), 7.37 (s, 1H), 6.91 (s, 1H), 4.16 (s, 2H), 3.78 (m, 2H), 3.21 (m, 2H), 2.44 (s, 3H), 2.26 (s, 3H), 1.78 (m, 2H). rhSyk=+++

Workup

  1. additionA sealed tube was charged with a stir bar
  2. customThe tube was evacuated
  3. additionFully degassed t-amyl alcohol (0.83 ml) was added
  4. customthe tube was sealed
  5. additionThe resulting slurry was diluted with methanol
  6. customabsorbed onto 1.5 g of silica
  7. custompurified via silica gel chromatography (0-20% methanol in ethyl acetate)

Sources & evidence

ORD record
ord-a39bda13939a46bfba90f9cc6fa682af
Source dataset
uspto-grants-2014_05
Patent number
US08735417B2

Reaction notes

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