Diisopropylethylamine → HCID 68157707, compound

HRID 243432Notes

Reaction equation

HRID 243432 reaction equation
Cl.Cl.[F:3][C:4]1[CH:5]=[CH:6][C:7]2[N:11]=[C:10]([C@@H:12]([NH2:14])[CH3:13])[N:9]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:8]=2[CH:21]=1.Cl[C:23]1[C:28]([C:29]#[N:30])=[C:27]([CH3:31])[N:26]=[CH:25][CH:24]=1.C(N(C(C)C)CC)(C)C>C(O)(C)C.CCOC(C)=O>[F:3][C:4]1[CH:5]=[CH:6][C:7]2[N:11]=[C:10]([C@@H:12]([NH:14][C:23]3[C:28]([C:29]#[N:30])=[C:27]([CH3:31])[N:26]=[CH:25][CH:24]=3)[CH3:13])[N:9]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:8]=2[CH:21]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 67125855HCID 67125855, compoundHCID 68157580(S)-1-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride

Product 1

HCID 68157707HCID 68157707, compoundYield 24.6%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

(S)-1-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride (0.083 g, 0.25 mmol), 4-chloro-2-methylnicotinonitrile (0.035 g, 0.23 mmol) and diisopropylethylamine (0.160 mL, 0.92 mmol) in isopropanol (1 mL) was heated to 80° C. in a sealed tube under argon for 2 h then at 75° C. for 86 h. The reaction mixture was cooled, diluted with EtOAc (20 mL) and washed with water (10 mL). The organic extracts were dried (Na2SO4), evaporated to dryness and purified by column chromatography (Si—PCC, gradient 0-8% (9:1 MeOH/0.880 NH3) in DCM). Product containing fractions were evaporated and freeze dried to give 340 as a pale brown solid, (21 mg, 24%). LCMS (Method C): RT 3.11 min [M+H]+ 372.08. 1H NMR δ (ppm DMSO-d6): 7.98 (1H, d, J=6.15 Hz), 7.77 (1H, dd, J=8.82, 4.86 Hz), 7.52-7.50 (5H, m), 7.12-7.11 (2H, m), 6.85 (1H, dd, J=8.91, 2.51 Hz), 6.40 (1H, d, J=6.24 Hz), 5.11 (1H, dq, J=7.04 Hz), 2.41 (3H, s), 1.56 (3H, d, J=6.64 Hz)

Workup

  1. temperatureThe reaction mixture was cooled
  2. washwashed with water (10 mL)
  3. dry with materialThe organic extracts were dried (Na2SO4)
  4. customevaporated to dryness
  5. custompurified by column chromatography (Si—PCC, gradient 0-8% (9:1 MeOH/0.880 NH3) in DCM)
  6. additionProduct containing fractions
  7. customwere evaporated
  8. customfreeze dried

Sources & evidence

ORD record
ord-c61e3453d81c44f9b2e010c49c026f78
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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