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

HRID 1028124Notes

Reaction equation

HRID 1028124 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]([O:29][CH3:30])[C:26]([Cl:31])=[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:31][C:26]1[C:27]([O:29][CH3:30])=[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 497617462,5-Dichloro-4-methoxypyrimidineHCID 67236328HCID 67236328, compound2×

Product 1

HCID 710753314-(5-{3-[(5-Chloro-4-methoxypyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-1,4-diazepan-2-oneYield 403.2%

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, 0.248 mmol), 2,5-dichloro-4-methoxypyrimidine (44 mg, 0.248 mmol), potassium carbonate (69 mg, 0.496 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 44 mg (1.0 mmol, 40% yield) of 4-(5-{3-[(5-chloro-4-methoxypyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-1,4-diazepan-2-one as a light yellow solid. MS APCI: [M+H]m/z 445.1. 1H NMR (500 MHz, dmso) δ 9.72 (s, 1H), 8.30 (s, 1H), 7.77 (s, 1H), 7.59 (t, J=5.0 Hz, 1H), 7.48 (s, 1H), 7.30 (s, 1H), 6.95 (s, 1H), 4.15 (s, 2H), 4.05 (s, 3H), 3.78 (m, 2H), 3.21 (m, 2H), 2.26 (s, 3H), 1.77 (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-ac7174a275dc4c4a980aa0f2cfe49fff
Source dataset
uspto-grants-2014_05
Patent number
US08735417B2

Reaction notes

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