Diisopropylethylamine → 4-Amino-6-[(S)-1-(6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)-ethylamino]-pyrimidine-5-carbonitrile

HRID 243387Notes

Reaction equation

HRID 243387 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.[NH2:22][C:23]1[C:28]([C:29]#[N:30])=[C:27](Cl)[N:26]=[CH:25][N:24]=1.CCN(C(C)C)C(C)C>CC(O)C>[NH2:22][C:23]1[C:28]([C:29]#[N:30])=[C:27]([NH:14][C@H:12]([C:10]2[N:9]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:8]3[CH:21]=[C:4]([F:3])[CH:5]=[CH:6][C:7]=3[N:11]=2)[CH3:13])[N:26]=[CH:25][N:24]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 122782624-Amino-6-chloropyrimidine-5-carbonitrileHCID 68157580(S)-1-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride

Product 1

HCID 534824624-Amino-6-[(S)-1-(6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)-ethylamino]-pyrimidine-5-carbonitrileYield 65%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
90 °C

Procedure

(S)-1-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride (328 mg, 1.00 mmol) was placed in a sealed tube with 4-amino-6-chloropyrimidine-5-carbonitrile (154.5 mg, 1.00 mol), DIPEA (0.7 mL, 4.00 mol) and IPA (1 mL). The tube was flushed with argon, sealed and the contents heated at 90° C. for 16 h. The cooled mixture was evaporated then diluted with EtOAc and water. The organic layer was washed with brine, dried (MgSO4) and evaporated. The crude residue was purified by chromatography on silica (Si—PCC, 1-80% EtOAc in DCM). The product containing fractions were pooled and evaporated almost to dryness. The residue was triturated in ether to afford 246 as a cream solid (240 mg, 65%). 1H NMR (CDCl3, 400 MHz): δ 8.01 (1H, s), 7.69 (1H, dd, J=8.8, 4.7 Hz), 7.59-7.49 (3H, m), 7.43-7.36 (2H, m), 7.02 (1H, td, J=9.2, 1.1 Hz), 6.77 (1H, dd, J=8.6, 2.4 Hz), 6.18 (1H, d, J=7.5 Hz), 5.52 (1H, quin, J=7.2 Hz), 5.30 (2H, br s), 1.54 (3H, d, J=6.9 Hz). LCMS (Method K): RT 3.80 min [M+H]+ 374

Workup

  1. customThe tube was flushed with argon
  2. customsealed
  3. customThe cooled mixture was evaporated
  4. additionthen diluted with EtOAc and water
  5. washThe organic layer was washed with brine
  6. dry with materialdried (MgSO4)
  7. customevaporated
  8. customThe crude residue was purified by chromatography on silica (Si—PCC, 1-80% EtOAc in DCM)
  9. additionThe product containing fractions
  10. customevaporated almost to dryness
  11. customThe residue was triturated in ether

Sources & evidence

ORD record
ord-c1c11e6be87c4e5cb53b955e53d52344
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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