2,2,2-Trifluoroethanol → 5-{9-Chloro-6-[1-(2,2,2-trifluoroethoxy)propyl]-3,4-dihydropyrimido[1,2-a]benzimidazol-1(2H)-yl}-N,N,6-trimethylpyridin-2-amine

HRID 1399093Notes

Reaction equation

HRID 1399093 reaction equation
[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[C:16]([CH3:24])=[N:17][C:18]([N:21]([CH3:23])[CH3:22])=[CH:19][CH:20]=4)[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH:25]([OH:28])[CH2:26][CH3:27])=[CH:4][CH:3]=1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C(P)CCC.[F:52][C:53]([F:57])([F:56])[CH2:54]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]([N:21]([CH3:23])[CH3:22])=[N:17][C:16]=4[CH3:24])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH:25]([O:28][CH2:54][C:53]([F:57])([F:56])[F:52])[CH2:26][CH3:27])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 64092,2,2-TrifluoroethanolHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 2784062ButylphosphineHCID 577861351-{9-Chloro-1-[6-(dimethylamino)-2-methylpyridin-3-yl]-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl}propan-1-ol

Product 1

HCID 577861105-{9-Chloro-6-[1-(2,2,2-trifluoroethoxy)propyl]-3,4-dihydropyrimido[1,2-a]benzimidazol-1(2H)-yl}-N,N,6-trimethylpyridin-2-amineYield 36%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 1-{9-chloro-1-[6-(dimethylamino)-2-methylpyridin-3-yl]-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl}propan-1-ol (71.1 mg, 0.178 mmol), 1,1′-(azodicarbonyl)dipiperidine (89.7 mg, 0.355 mmol) and n-butylphosphine (71.8 mg, 0.355 mmol) in tetrahydrofuran (2.0 mL) was stirred at room temperature for 15 min. 2,2,2-Trifluoroethanol (178 mg, 1.78 mmol) was added to the mixture, and the mixture was stirred at 60° C. for 7 hr. The mixture was concentrated in vacuo, and the residue was purified by flash column chromatography on silica gel eluting with a 35-80% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the solid, which was recrystallized from ethyl acetate/diisopropyl ether to give the title compound as a colorless crystal (30.8 mg, 0.0639 mmol, 36%)

Workup

  1. stirringthe mixture was stirred at 60° C. for 7 hr
  2. concentrationThe mixture was concentrated in vacuo
  3. customthe residue was purified by flash column chromatography on silica gel eluting with a 35-80% ethyl acetate/n-hexane gradient mixture
  4. concentrationThe filtrate was concentrated in vacuo
  5. customto give the solid, which
  6. customwas recrystallized from ethyl acetate/diisopropyl ether

Sources & evidence

ORD record
ord-c46dc183abe04900b814ac472ac47ecf
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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