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

HRID 243445Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 243445
[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][CH: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:14]=[CH:15][CH:16]=[CH:17][CH:18]=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

Komponenten

6

Edukt 3

HCID 81531DiisopropylethylamineHCID 58459302(S)-1-(6-Fluoro-1-phenyl-1H-benzo[D]imidazol-2-YL)ethanamineHCID 717413792-Amino-4-chloropyrimidine-5-carbonitrile

Produkt 1

HCID 681580102-Amino-4-[(S)-1-(6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)-ethylamino]-pyrimidine-5-carbonitrileAusbeute 63 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 3776IsopropanolLösungsmittel

Versuchsvorschrift

A mixture of (S)-1-(6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine.2HCl (85 mg, 0.259 mmol), 2-amino-4-chloropyrimidine-5-carbonitrile (40 mg, 0.26 mmol) and DIPEA (222 μL, 1.29 mmol) in IPA (0.75 mL) was heated at 90° C. in a sealed vial for 21 h. After cooling to RT, the crude mixture was diluted with MeOH and loaded into 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 DCM) followed by trituration from EtOAc/Et2O/cyclohexane to afford 362 as a white solid (61 mg, 63%). LCMS (Method K): RT 3.47 min [M+H]+ 374.02. 1H NMR (DMSO-d6, 400 MHz): δ 8.08 (1H, s), 7.74 (1H, dd, J=8.80, 4.85 Hz), 7.68 (1H, d, J=7.49 Hz), 7.58-7.52 (5H, m), 7.16-6.70 (4H, m), 5.51 (1H, m), 1.47 (3H, d, J=6.80 Hz)

Aufarbeitung

  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 DCM)

Quellen und Nachweise

ORD-Eintrag
ord-2c8a707762df45739d45037c21354301
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08653089B2

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