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

HRID 243450Notes

Reaction equation

HRID 243450 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C@@H:10]([NH2:12])[CH3:11])[N:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=3)[C:6]=2[CH:19]=1.[NH2:20][C:21]1[N:26]=[C:25](Cl)[C:24]([C:28]#[N:29])=[CH:23][N:22]=1.CCN(C(C)C)C(C)C>CC(O)C.CO>[NH2:20][C:21]1[N:26]=[C:25]([NH:12][C@H:10]([C:8]2[N:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=3)[C:6]3[CH:19]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=3[N:9]=2)[CH3:11])[C:24]([C:28]#[N:29])=[CH:23][N:22]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 68157234(S)-1-(6-Fluoro-1-pyrid-2-yl-1H-benzoimidazol-2-yl)ethylamineHCID 717413792-Amino-4-chloropyrimidine-5-carbonitrile

Product 1

HCID 681581702-Amino-4-[(S)-1-(6-fluoro-1-pyridin-2-yl-1H-benzoimidazol-2-yl)-ethylamino]-pyrimidine-5-carbonitrileYield 39%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 3776IsopropanolSolvent

Procedure

A mixture of (S)-1-(6-fluoro-1-pyridin-2-yl-1H-benzoimidazol-2-yl)ethylamine.2HCl (164 mg, 0.50 mmol), 2-amino-4-chloropyrimidine-5-carbonitrile (77 mg, 0.50 mmol) and DIPEA (427 μL, 2.49 mmol) in IPA (1 mL) was heated at 90° C. in a sealed vial for 17 h. After cooling to RT, the reaction mixture was diluted with MeOH and loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH followed by 2M NH3/MeOH. The basic fractions were combined, concentrated in vacuo and the resulting residue purified by column chromatography (Si—PCC, gradient 0-100% EtOAc in cyclohexane) followed by trituration from Et2O to afford 367 as a white solid (72 mg, 39%). LCMS (Method K): RT 3.06 min [M+H]+ 375.00. 1H NMR (DMSO-d6, 400 MHz): δ 8.59 (1H, m), 8.06 (2H, m), 7.77 (2H, m), 7.68 (1H, d, J=7.41 Hz), 7.48 (1H, m), 7.19-6.80 (4H, m), 5.85 (1H, m), 1.52 (3H, d, J=6.81 Hz

Workup

  1. washThe cartridge was washed with MeOH
  2. concentrationconcentrated in vacuo
  3. customthe resulting residue purified by column chromatography (Si—PCC, gradient 0-100% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-de25a0a669bc40329f988bc415f83443
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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