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 2175417ノート

反応式

HRID 2175417 の反応式
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]

参加物

8

反応物 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

生成物 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)carbamate収率 99.2%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
85 °C

実験手順

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.

後処理

  1. filtrationfiltered
  2. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-129b659238bb44ecbe90d2caf4204167
出典データセット
uspto-grants-2015_06
特許番号
US09062059B2

反応ノート

読み込み中…