Sodium triacetoxyborohydride → 4-[((1R,3S)-3-Isopropyl-3-{[7-(trifluoromethyl)-3,4-dihydroisoquinolin-2(1H)-yl]carbonyl}cyclopentyl)amino]-1-pyrimidin-2-ylcyclohexanol

HRID 969568ノート

反応式

HRID 969568 の反応式
[OH:1][C:2]1([C:9]2[N:14]=[CH:13][CH:12]=[CH:11][N:10]=2)[CH2:7][CH2:6][C:5](=O)[CH2:4][CH2:3]1.[CH:15]([C@:18]1([C:24]([N:26]2[CH2:35][CH2:34][C:33]3[C:28](=[CH:29][C:30]([C:36]([F:39])([F:38])[F:37])=[CH:31][CH:32]=3)[CH2:27]2)=[O:25])[CH2:22][CH2:21][C@@H:20]([NH2:23])[CH2:19]1)([CH3:17])[CH3:16].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH:15]([C@:18]1([C:24]([N:26]2[CH2:35][CH2:34][C:33]3[C:28](=[CH:29][C:30]([C:36]([F:39])([F:37])[F:38])=[CH:31][CH:32]=3)[CH2:27]2)=[O:25])[CH2:22][CH2:21][C@@H:20]([NH:23][CH:5]2[CH2:6][CH2:7][C:2]([C:9]3[N:14]=[CH:13][CH:12]=[CH:11][N:10]=3)([OH:1])[CH2:3][CH2:4]2)[CH2:19]1)([CH3:17])[CH3:16]

参加物

5

反応物 3

HCID 5049666Sodium triacetoxyborohydride2 回HCID 58784490((1S,3R)-3-amino-1-isopropylcyclopentyl)(7-(trifluoromethyl)-3,4-dihydroisoquinolin-2(1H)-yl)methanoneHCID 590174304-Hydroxy-4-pyrimidin-2-yl-cyclohexanone

生成物 1

HCID 115046884-[((1R,3S)-3-Isopropyl-3-{[7-(trifluoromethyl)-3,4-dihydroisoquinolin-2(1H)-yl]carbonyl}cyclopentyl)amino]-1-pyrimidin-2-ylcyclohexanol

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of 4-hydroxy-4-pyrimidin-2-yl-cyclohexanone (59.8 mg, 0.31 mmol) and (1R,3S)-3-isopropyl-3-{[7-(trifluoromethyl)-3,4-dihydroisoquinolin-2(1H)-yl]carbonyl}cyclopentanamine (110 mg, 0.31 mmol) of Step C-2 of Example 1 in CH2Cl2(10 mL) was added sodium triacetoxyborohydride (131 mg, 0.62 mmol). After being stirred overnight, more sodium triacetoxyborohydride was added to bring the equivalents of the reducing agent to 5 equivalents. After stirring for another 5 hrs, the reaction was quenched with aqueous NaOH. The resulting solution was extracted with EtOAc three times. The combined extracts were dried over MgSO4 and concentrated. Purification by flash chromatography followed by HPLC gave two isomers. Isomer 1 and isomer 2: MS calculated for C29H37F3N4O2: (M+H)+531; found 531.1.

後処理

  1. stirringAfter stirring for another 5 hrs
  2. customthe reaction was quenched with aqueous NaOH
  3. extractionThe resulting solution was extracted with EtOAc three times
  4. dry with materialThe combined extracts were dried over MgSO4
  5. concentrationconcentrated
  6. customPurification by flash chromatography
  7. customgave two isomers

出典と根拠

ORDレコード
ord-bf1f05c5205b4b37a683c010801c4fa6
出典データセット
uspto-grants-2007_12
特許番号
US07307086B2

反応ノート

読み込み中…