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 1872770노트

반응식

HRID 1872770 반응식
[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]

참가 물질

9

반응물 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

생성물 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)piperidine수율 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)piperidine수율 2.2%

시약·촉매·용매 3

HCID 11026Titanium isopropoxide촉매HCID 702Ethanol용매HCID 6344Dichloromethane용매2회

실험 절차

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.).

후처리

  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

출처 및 근거

ORD 기록
ord-e6a0717aba724ebcb34fb76e398ac729
출처 데이터셋
uspto-grants-2000_08
특허 번호
US06110939

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