Diisopropylethylamine → 4-Amino-6-{(S)-1-[6-fluoro-1-(5-fluoro-pyridin-3-yl)-1H-benzoimidazol-2-yl]-propylamino}-pyrimidine-5-carbonitrile

HRID 243439Notes

Reaction equation

[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C@@H:10]([NH2:13])[CH2:11][CH3:12])[N:7]([C:14]3[CH:15]=[N:16][CH:17]=[C:18]([F:20])[CH:19]=3)[C:6]=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:13][C@H:10]([C:8]2[N:7]([C:14]3[CH:15]=[N:16][CH:17]=[C:18]([F:20])[CH:19]=3)[C:6]3[CH:21]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=3[N:9]=2)[CH2:11][CH3:12])[N:26]=[CH:25][N:24]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of (S)-1-[6-fluoro-1-(5-fluoropyridin-3-yl)-1H-benzoimidazol-2-yl]propylamine (88 mg, 0.32 mmol), 4-amino-6-chloro-5-cyanopyrimidine (49 mg, 0.32 mmol) and DIPEA (0.11 mL, 0.64 mmol) in IPA (1 mL) was heated for 5.5 h at 90° C. After cooling to RT, the volatiles were removed in vacuo and the resulting residue was purified by column chromatography (Si—PPC, gradient 0-5% 2M NH3/MeOH in EtOAc) to afford 350 as a pale yellow solid (83 mg, 64%). LCMS (Method K): RT 3.67 min [M+H]+ 407.0. 1H NMR (CDCl3, 400 MHz): δ 8.68 (1H, d, J=2.7 Hz), 8.60 (1H, br s), 8.01 (1H, s), 7.70 (1H, dd, J=9.0, 4.9 Hz), 7.67 (1H, br s), 7.06 (1H, app. td, J=9.2, 2.4 Hz), 6.79 (1H, dd, J=8.3, 2.4 Hz), 6.00 (1H, d, J=8.0 Hz), 5.40 (2H, s), 5.31 (1H, dt, J=8.0, 7.3 Hz), 2.05 (1H, dqd, J=14.7, 7.4, 7.3 Hz), 1.97 (1H, dqd, J=14.7, 7.4, 7.3 Hz), 0.86 (3H, t, J=7.4 Hz)

Workup

temperatureAfter cooling to RT
customthe volatiles were removed in vacuo
customthe resulting residue was purified by column chromatography (Si—PPC, gradient 0-5% 2M NH3/MeOH in EtOAc)

Sources & evidence

ORD record: ord-22989118a7064b749306a45219ddb086
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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