Cesium carbonate → 2-(3-{6-[(2,3-Dihydro-benzofuran-2-ylmethyl)-amino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid

HRID 216254노트

반응식

HRID 216254 반응식
Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[N:5]=[C:4]([NH:10][CH2:11][CH:12]2[CH2:16][C:15]3[CH:17]=[CH:18][CH:19]=[CH:20][C:14]=3[O:13]2)[CH:3]=1.[C:21]([C:24]([C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[CH:31][CH:32]=1)([CH3:26])[CH3:25])([OH:23])=[O:22].C([O-])([O-])=O.[Cs+].[Cs+]>COCCOC.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[O:13]1[C:14]2[CH:20]=[CH:19][CH:18]=[CH:17][C:15]=2[CH2:16][CH:12]1[CH2:11][NH:10][C:4]1[N:5]=[C:6]([O:8][CH3:9])[N:7]=[C:2]([C:29]2[CH:28]=[C:27]([C:24]([CH3:26])([CH3:25])[C:21]([OH:23])=[O:22])[CH:32]=[CH:31][CH:30]=2)[CH:3]=1

참가 물질

7

반응물 3

HCID 10796Cesium carbonateHCID 442489972-(3-Boronophenyl)-2-methylpropanoic acidHCID 86615711(6-Chloro-2-methoxy-pyrimidin-4-yl)-(2,3-dihydro-benzofuran-2-ylmethyl)-amine

생성물 1

HCID 576359972-(3-{6-[(2,3-Dihydro-benzofuran-2-ylmethyl)-amino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid수율 58.1%

시약·촉매·용매 3

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 962Water용매2회HCID 80711,2-Dimethoxyethane용매

반응 조건

온도
85 °C

실험 절차

A mixture of (6-chloro-2-methoxy-pyrimidin-4-yl)-(2,3-dihydro-benzofuran-2-ylmethyl)-amine (167 mg, 0.57 mmol), 3-(1-carboxy-1-methyl-ethyl)-phenyl-boronic acid (155 mg, 0.75 mmol), and Cs2CO3 (0.46 g, 1.43 mmol) in ethylene glycol dimethyl ether (8 mL) and water (2 mL) is degassed by bubbling with Ar gas for 5 minutes, and treated with tetrakis(triphenylphosphine) palladium(0) (33 mg, 0.03 mmol) at room temperature. The mixture is heated at 85° C. for 3 h. The mixture is diluted with H2O (20 mL), and extracted with EtOAc (10 mL). The aqueous layer is separated, acidified to pH 2.5 with 1M HCl solution, and extracted with EtOAc (2×10 mL). The extracts are dried (MgSO4), filtered through a short pad of SiO2 to afford 2-(3-{6-[(2,3-dihydro-benzofuran-2-ylmethyl)-amino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid (139 mg, Example 90). LCMS: RT=2.05 minutes; MS: 420 (M+H); 1H NMR (300 MHz, DMSO-d6) □12.4 (1H, s), 8.05-7.8 (2H, m), 7.5-7.1 (5H, m), 6.8-6.75 (2H, m), 5 (1H, s), 4 (3H, brs), 3.65 (2H, brs), 3.4-2.95 (2H, m), 1.48 (6H, s).

후처리

  1. customis degassed
  2. customby bubbling with Ar gas for 5 minutes
  3. extractionextracted with EtOAc (10 mL)
  4. customThe aqueous layer is separated
  5. extractionextracted with EtOAc (2×10 mL)
  6. dry with materialThe extracts are dried (MgSO4)
  7. filtrationfiltered through a short pad of SiO2

출처 및 근거

ORD 기록
ord-3d82b5a7fb564148b7a0589bf50cf653
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08193183B2

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