Water → (+/-)-cis-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[[3-(2-furanylmethyl)-3H-imidazo-[4,5-b]pyridin-2-yl]amino]-2-(phenylmethyl)piperidine

HRID 1872770ノート

反応式

HRID 1872770 の反応式
[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=1)[C:6]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH:9]1[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:7].[O:31]1[CH:35]=[CH:34][CH:33]=[C:32]1[CH2:36][N:37]1[C:41]2=[N:42][CH:43]=[CH:44][CH:45]=[C:40]2[N:39]=[C:38]1[NH2:46].C([BH3-])#N.[Na+].O>C(Cl)Cl.C(O)C.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[F:26][C:25]([F:28])([F:27])[C:23]1[CH:22]=[C:5]([CH:4]=[C:3]([C:2]([F:30])([F:1])[F:29])[CH:24]=1)[C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([NH:46][C:38]2[N:37]([CH2:36][C:32]3[O:31][CH:35]=[CH:34][CH:33]=3)[C:41]3=[N:42][CH:43]=[CH:44][CH:45]=[C:40]3[N:39]=2)[CH2:10][C@@H:9]1[CH2:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)=[O:7].[F:26][C:25]([F:28])([F:27])[C:23]1[CH:22]=[C:5]([CH:4]=[C:3]([C:2]([F:30])([F:1])[F:29])[CH:24]=1)[C:6]([N:8]1[CH2:13][CH2:12][C@@H:11]([NH:46][C:38]2[N:37]([CH2:36][C:32]3[O:31][CH:35]=[CH:34][CH:33]=3)[C:41]3=[N:42][CH:43]=[CH:44][CH:45]=[C:40]3[N:39]=2)[CH2:10][C@@H:9]1[CH2:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)=[O:7]

参加物

9

反応物 4

HCID 962WaterHCID 5003444Sodium cyanoborohydrideHCID 11026356(+/-)-1-[3,5-Bis(trifluoromethyl)benzoyl]-2-(phenylmethyl)-4-piperidinoneHCID 156239903-(2-furanylmethyl)-3H-imidazo[4,5-b]pyridin-2-amine

生成物 2

HCID 86755700(+/-)-cis-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[[3-(2-furanylmethyl)-3H-imidazo-[4,5-b]pyridin-2-yl]amino]-2-(phenylmethyl)piperidine収率 19.4%HCID 86755701(+/-)-trans-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[[3-(2-furanylmethyl)-3H-imidazo[4,5-b]pyridin-2-yl]amino]-2-(phenylmethyl)piperidine収率 2.2%

試薬・触媒・溶媒 3

HCID 11026Titanium isopropoxide触媒HCID 702Ethanol溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

A mixture of (±)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(phenylmethyl)-4-piperidinone (4.29 g), 3-(2-furanylmethyl)-3H-imidazo[4,5-b]pyridin-2-amine (2.14 g) and titanium(IV)isopropoxide (3.41 g) in CH2Cl2 (5 ml) was stirred at RT for 3 hours. A mixture of sodium cyanoborohydride (0.628 g) in ethanol (5 ml) was added. The mixture was stirred at RT overnight. Water (5 ml) and CH2Cl2 (300 ml) were added. The mixture was stirred for 15 minutes. The biphasic mixture was dried, filtered and the filtrate was evaporated. The residue was purified by HPLC (eluent: 0.5% NH4OC(O)CH3 /CH3CN 40/60). Two desired fractions were collected and their solvent was evaporated. Each residue was dried and ground, yielding 1.22 g (19.4%) of (±)-cis-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[[3-(2-furanylmethyl)-3H-imidazo-[4,5-b]pyridin-2-yl]amino]-2-(phenylmethyl)piperidine (comp. 112; mp. 108.7° C.) and 0.14 g (2.2%) of (±)-trans-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[[3-(2-furanylmethyl)-3H-imidazo[4,5-b]pyridin-2-yl]amino]-2-(phenylmethyl)piperidine (comp. 113; mp. 108.3° C.).

後処理

  1. additionwas added
  2. stirringThe mixture was stirred at RT overnight
  3. stirringThe mixture was stirred for 15 minutes
  4. customThe biphasic mixture was dried
  5. filtrationfiltered
  6. customthe filtrate was evaporated
  7. customThe residue was purified by HPLC (eluent: 0.5% NH4OC(O)CH3 /CH3CN 40/60)
  8. customTwo desired fractions were collected
  9. customtheir solvent was evaporated
  10. customEach residue was dried

出典と根拠

ORDレコード
ord-e6a0717aba724ebcb34fb76e398ac729
出典データセット
uspto-grants-2000_08
特許番号
US06110939

反応ノート

読み込み中…