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 1872770Notes

Reaction equation

HRID 1872770 reaction equation
[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]

Participants

9

Reactant 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

Product 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)piperidineYield 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)piperidineYield 2.2%

Reagents, catalysts & solvents 3

HCID 11026Titanium isopropoxideCatalystHCID 702EthanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

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.).

Workup

  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

Sources & evidence

ORD record
ord-e6a0717aba724ebcb34fb76e398ac729
Source dataset
uspto-grants-2000_08
Patent number
US06110939

Reaction notes

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