2,2,2-Trifluoroethanol → 9-Chloro-6-[cyclopropyl(2,2,2-trifluoroethoxy)methyl]-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole

HRID 1399317Notes

Reaction equation

HRID 1399317 reaction equation
[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=4[Cl:22])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH:23]([CH:25]2[CH2:27][CH2:26]2)[OH:24])=[CH:4][CH:3]=1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C(P(CCCC)CCCC)CCC.[F:59][C:60]([F:64])([F:63])[CH2:61]O>O1CCCC1>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=4[Cl:22])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH:23]([CH:25]2[CH2:27][CH2:26]2)[O:24][CH2:61][C:60]([F:64])([F:63])[F:59])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 64092,2,2-TrifluoroethanolHCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 57786088[9-Chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl](cyclopropyl)methanol

Product 1

HCID 577862829-Chloro-6-[cyclopropyl(2,2,2-trifluoroethoxy)methyl]-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazoleYield 57.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of [9-chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl](cyclopropyl)methanol (150 mg, 0.355 mmol), 1,1′-(azodicarbonyl)dipiperidine (179 mg, 0.709 mmol) in tetrahydrofuran (7.5 mL) was added tri(n-butyl)phosphine (0.177 mL, 0.709 mmol) at room temperature. After the mixture was stirred at room temperature for 10 min under nitrogen atmosphere, 2,2,2-trifluoroethanol (0.259 mL, 3.55 mmol) was added to the reaction mixture. The mixture was stirred at 65° C. for 15 hr under nitrogen atmosphere. The mixture was concentrated in vacuo and diethyl ether was added to the residue. The solid was removed by filtration and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with a 10-30% ethyl acetate/n-hexane gradient mixture and recrystallization from 2-propanol/n-hexane to give the title compound (102.9 mg, 0.204 mmol, 57%) as colorless crystals.

Workup

  1. stirringThe mixture was stirred at 65° C. for 15 hr under nitrogen atmosphere
  2. concentrationThe mixture was concentrated in vacuo and diethyl ether
  3. additionwas added to the residue
  4. customThe solid was removed by filtration
  5. concentrationthe filtrate was concentrated in vacuo
  6. customThe residue was purified by flash chromatography on silica gel eluting with a 10-30% ethyl acetate/n-hexane gradient mixture and recrystallization from 2-propanol/n-hexane

Sources & evidence

ORD record
ord-e9b01755051941e180e80f6ee67dc6f4
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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