Cesium carbonate → tert-Butyl-6-(((1S,2S)-2-(5-(2-hydroxypropan-2-yl)pyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-4-yl((5-methyl-1,3,4-thiadiazol-2-yl)methyl)carbamate

HRID 2175417노트

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HRID 2175417 반응식
Cl[C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([O:9][CH2:10][C@H:11]2[CH2:13][C@@H:12]2[C:14]2[N:19]=[CH:18][C:17]([C:20]([OH:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=2)[CH:3]=1.[CH3:24][C:25]1[S:29][C:28]([CH2:30][NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[N:27][N:26]=1.C([O-])([O-])=O.[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:34]([O:33][C:32](=[O:38])[N:31]([C:2]1[CH:3]=[C:4]([O:9][CH2:10][C@H:11]2[CH2:13][C@@H:12]2[C:14]2[CH:15]=[CH:16][C:17]([C:20]([OH:23])([CH3:22])[CH3:21])=[CH:18][N:19]=2)[N:5]=[C:6]([CH3:8])[N:7]=1)[CH2:30][C:28]1[S:29][C:25]([CH3:24])=[N:26][N:27]=1)([CH3:37])([CH3:36])[CH3:35]

참가 물질

8

반응물 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 59892191Tert-butyl ((5-methyl-1,3,4-thiadiazol-2-yl)methyl)carbamateHCID 867295742-(6-((1S,2S)-2-((6-chloro-2-methylpyrimidin-4-yloxy)methyl)cyclopropyl)pyridin-3-yl)propan-2-ol

생성물 1

HCID 90332200tert-Butyl-6-(((1S,2S)-2-(5-(2-hydroxypropan-2-yl)pyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-4-yl((5-methyl-1,3,4-thiadiazol-2-yl)methyl)carbamate수율 99.2%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

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온도
85 °C

실험 절차

The mixture of 8-3 (60 mg, 0.18 mmol), 8-4 (50 mg, 0.22 mmol), Cs2CO3 (88 mg, 0.27 mmol), Pd(OAc)2 (8.1 mg, 0.036 mmol), BINAP (25 mg, 0.040 mmol) in toluene (2.0 mL) was heated at 85° C. for overnight. Then the reaction mixture was diluted with EtOAc (20 mL), filtered and concentrated in vacuo to give crude product (94 mg) which was used for next step without further purification. LRMS (ES) calculated M+H for C26H34N6O4S: 527.24. Found: 527.2.

후처리

  1. filtrationfiltered
  2. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-129b659238bb44ecbe90d2caf4204167
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09062059B2

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