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

HRID 1028122노트

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HRID 1028122 반응식
[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

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 9811564Bis(dibenzylideneacetone)palladium촉매

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온도
90 °C

실험 절차

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=+++.

후처리

  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)

출처 및 근거

ORD 기록
ord-86ee5f867d744812935d81d32ab34256
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08735417B2

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