Tributylphosphine → HCID 57785994, compound

HRID 1628832Notes

Reaction equation

HRID 1628832 reaction equation
[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[C:16]([CH3:23])=[N:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=4)[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH:24]([CH:26]2[CH2:28][CH2:27]2)[OH:25])=[CH:4][CH:3]=1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C(P(CCCC)CCCC)CCC.[F:60][CH:61]([F:64])[CH2:62]O>O1CCCC1>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[C:16]([CH3:23])=[N:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=4)[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH:24]([CH:26]2[CH2:28][CH2:27]2)[O:25][CH2:62][CH:61]([F:64])[F:60])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 1361872,2-Difluoroethan-1-olHCID 57786231HCID 57786231, compound

Product 1

HCID 57785994HCID 57785994, compoundYield 47.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of [9-chloro-1-(6-methoxy-2-methylpyridin-3-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl](cyclopropyl)methanol (112.9 mg, 0.283 mmol) in tetrahydrofuran (2.8 mL) was added 1,1′-(azodicarbonyl)dipiperidine (142.8 mg, 0.566 mmol) and tributylphosphine (141.0 μL, 0.566 mmol). After 10 min, to the mixture was added 2,2-difluoroethanol (179.2 μL, 2.830 mmol). The reaction mixture was stirred at 60° C. for 4 hrs. The mixture was concentrated. To the residue was added diethyl ether and the precipitate was removed by filtration. The residue was purified by silica gel column chromatography eluting with a 0-50% ethyl acetate/n-hexane gradient mixture to give the mixture. The resulting solid was recrystallized from ethyl acetate/n-hexane to give the title compound as a colorless powder (62.0 mg, 0.134 mmol, 47%).

Workup

  1. concentrationThe mixture was concentrated
  2. additionTo the residue was added diethyl ether
  3. customthe precipitate was removed by filtration
  4. customThe residue was purified by silica gel column chromatography
  5. washeluting with a 0-50% ethyl acetate/n-hexane gradient mixture
  6. customto give the mixture
  7. customThe resulting solid was recrystallized from ethyl acetate/n-hexane

Sources & evidence

ORD record
ord-87f89ace1a2141c58afed599451c70a7
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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