Acetic Acid → HCID 86649778, compound

HRID 450182Notes

Reaction equation

HRID 450182 reaction equation
Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([N:9]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[N:11]=[C:10]2[CH:18]([F:20])[F:19])[N:3]=1.[NH2:21][C:22]1[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=1.[Li+].CC([N-]C(C)C)C.CC(O)=O>C1COCC1.O>[Cl:8][C:6]1[N:5]=[C:4]([N:9]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[N:11]=[C:10]2[CH:18]([F:20])[F:19])[N:3]=[C:2]([NH:21][C:22]2[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=2)[CH:7]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 100093-AminopyridineHCID 2724682Lithium diisopropylamideHCID 220368734,6-Dichloro-2-(2-difluoromethylbenzimidazol-1-yl)pyrimidine

Product 1

HCID 86649778HCID 86649778, compoundYield 67%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

1-(4,6-Dichloro-2-pyrimidinyl)-2-(difluoromethyl)-1H-benzimidazole (International Publ. No. WO 2002/088112, the disclosure of which is incorporated herein by reference in its entirety) (0.315 g, 1 mmol) was added to a mixture of 3-aminopyridine (0.28 g, 3 mmol) and LDA (1.5 mL, 2 M in THF, 3 mmol) in 10 mL THF at room temperature. After 10 min, the mixture was neutralized with HOAc, diluted with water, extracted with EtOAc, and dried (Na2SO4). Chromatography on silica, eluting with CH2Cl2/EtOAc (3:2) gave a solid, which was recrystallized from i-Pr2O to give 0.252 g (67% yield) of 6-chloro-2-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-N-(3-pyridinyl)-4-pyrimidinamine: mp (i-Pr2O) 233-236° C.; 1H NMR (DMSO-d6) δ 10.42 (br, 1H), 8.72 (d, J=2.3 Hz, 1H), 8.43 (dd, J=4.7, 1.4 Hz, 1H), 8.26 (m, 1H), 8.01 (ddd, J=8.3, 2.5, 1.5 Hz, 1H), 7.86 (m, 1H), 7.62 (t, JHF′=52.9 Hz, 1H), 7.48-7.42 (m, 3H), 6.86 (s, 1H); Anal. Calcd. for C17H11ClF2N6: C, 54.8; H, 3.0; N, 22.55. Found: C, 54.75; H, 3.0; N, 22.7%.

Workup

  1. extractionextracted with EtOAc
  2. dry with materialdried (Na2SO4)
  3. washChromatography on silica, eluting with CH2Cl2/EtOAc (3:2)
  4. customgave a solid, which
  5. customwas recrystallized from i-Pr2O

Sources & evidence

ORD record
ord-669e4bc03cfc4464b2b48727184f6042
Source dataset
uspto-grants-2013_07
Patent number
US08486939B2

Reaction notes

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