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

HRID 1028122Notes

Reaction equation

HRID 1028122 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]=[CH:27][C:26]([Cl:29])=[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:29][C:26]1[CH:25]=[N:24][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:28][CH:27]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 5906412,5-DichloropyrimidineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 67236328HCID 67236328, compound

Product 1

HCID 532513954-(5-{3-[(5-Chloropyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-1,4-diazepan-2-oneYield 48.1%

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 (100 mg, 0.331 mmol), 2,5-dichloropyrimidine (49.3 mg, 0.331 mmol), potassium carbonate (91 mg, 0.661 mmol), Pd2 dba3 (30.3 mg, 0.033 mmol), and XPhos (79 mg, 0.165 mmol). The tube was evacuated and backfilled with argon three times. Fully degassed t-amyl alcohol (1.1 ml) was added, the tube was sealed and heated at 90° C. for overnight. The slurry was then cooled to room temperature, diluted with methanol, absorbed onto 2 g of silica, and purified via silica gel chromatography (0-20% methanol in ethyl acetate) to afford 4-(5-{3-[(5-chloropyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-1,4-diazepan-2-one (66 mg, 0.159 mmol, 48.1% yield) as a bright yellow solid. MS APCI: [M+H]+ m/z 415.1. 1H NMR (500 MHz, DMSO) δ 9.80 (s, 1H), 8.55 (s, 2H), 7.60 (s, 2H), 7.46 (s, 1H), 7.41 (s, 1H), 6.93 (s, 1H), 4.16 (m, 2H), 3.78 (m, 2H), 3.20 (m, 2H), 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 (1.1 ml) was added
  4. customthe tube was sealed
  5. temperatureThe slurry was then cooled to room temperature
  6. additiondiluted with methanol
  7. customabsorbed onto 2 g of silica
  8. custompurified via silica gel chromatography (0-20% methanol in ethyl acetate)

Sources & evidence

ORD record
ord-86ee5f867d744812935d81d32ab34256
Source dataset
uspto-grants-2014_05
Patent number
US08735417B2

Reaction notes

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