Diisopropylethylamine → [(S)-1-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)-ethyl]-pyrido[3,2-d]pyrimidin-4-yl-amine

HRID 243421Notes

Reaction equation

HRID 243421 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:24]2[N:32]=[CH:31][CH:30]=[CH:29][C:25]=2[N:26]=[CH:27][N:28]=1.CCN(C(C)C)C(C)C>CC(O)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:24]4[N:32]=[CH:31][CH:30]=[CH:29][C:25]=4[N:26]=[CH:27][N:28]=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 131016394-Chloropyrido(3,2-d)pyrimidineHCID 68157580(S)-1-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride

Product 1

HCID 60162560[(S)-1-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)-ethyl]-pyrido[3,2-d]pyrimidin-4-yl-amine

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

(S)-1-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride (0.082 g, 0.25 mmol), 4-chloropyrido[3,2-d]pyrimidine (J. Med Chem, 1833, 1996) (0.035 g, 0.21 mmol) and DIPEA (0.174 mL, 1.0 mmol) in IPA (1 mL) was heated to 70° C. in a sealed tube under argon for 1 h. The reaction mixture was cooled, diluted with EtOAc (20 mL) and washed with water (2 mL). The aqueous was extracted with EtOAc (10 mL). The combined 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 317 as an off white solid, (15 mg, 18%). LCMS (Method C): RT 3.55 min [M+H]+ 385.05. 1H NMR δ (ppm) (DMSO-d6): 8.83 (1H, dd, J=4.24, 1.57 Hz), 8.63 (1H, d, J=7.55 Hz), 8.40 (1H, s), 8.11 (1H, dd, J=8.46, 1.57 Hz), 7.84 (1H, dd, J=8.47, 4.24 Hz), 7.74 (1H, dd, J=8.81, 4.85 Hz), 7.59 (2H, d, J=7.53 Hz), 7.50-7.50 (3H, m), 7.12 (1H, ddd, J=9.87, 8.81, 2.53 Hz), 6.86 (1H, dd, J=8.92, 2.51 Hz), 5.59 (1H, dq, J=7.09 Hz), 1.59 (3H, d, J=6.81 Hz)

Workup

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

Sources & evidence

ORD record
ord-6fa9ddb01c3442cbacd341faf3719eef
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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