Diisopropylethylamine → HCID 68157294, compound

HRID 243490Notes

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

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of (S)-1-[6-fluoro-1-(2-methyl-2H-pyrazol-3-yl)-1H-benzoimidazol-2-yl]ethylamine, (0.093 g, 0.359 mmol), 4-amino-6-chloropyrimidine-5-carbonitrile (0.078 g, 0.502 mmol) and DIPEA (0.12 mL, 0.646 mmol) in IPA (2 mL) was stirred at 80° C. in a sealed microwave tube for 16 h. After cooling, mixture was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH then concentrated in vacuo. Residue was purified by silica gel chromatography eluting with 100% DCM—8% (2M ammonia in methanol) in DCM to give 416 as a white solid (0.107 g, 79%). LCMS (Method K): RT 3.16, 3.28 min [M+H]+ 378.0. 1H NMR (DMSO-d6, 400 MHz): δ 7.92-7.87 (1H, s), 7.87-7.84 (1H, m), 7.75-7.75 (1H, m), 7.60-7.54 (1H, m), 7.30-7.19 (3H, m), 6.96 (1H, m), 6.61-6.44 (1H, m), 5.47-5.38 (1H, m), 3.59-3.53 (3H, m), 3.17 (0H, d, J=5.25 Hz), 1.58-1.51 (3H, m). Signals split due to presence of rotamers/tautomers

Workup

temperatureAfter cooling
washwas washed with MeOH
washthe product eluted with 2M NH3/MeOH
concentrationthen concentrated in vacuo
customResidue was purified by silica gel chromatography
washeluting with 100% DCM—8% (2M ammonia in methanol) in DCM

Sources & evidence

ORD record: ord-076232f54c314b7f875d995ae43ad818
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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