Triethylamine → (S)-2-Amino-4-methyl-6-((1-(1-methyl-6-(tetrahydro-2H-pyran-4-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)amino)pyrimidine-5-carbonitrile

HRID 75328Notes

Reaction equation

[CH3:1][N:2]1[C:10]2[C:5](=[N:6][C:7]([C@@H:17]([NH2:19])[CH3:18])=[C:8]([CH:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)[CH:9]=2)[CH:4]=[CH:3]1.[NH2:20][C:21]1[N:26]=[C:25](Cl)[C:24]([C:28]#[N:29])=[C:23]([CH3:30])[N:22]=1.CCN(CC)CC>CN(C=O)C>[NH2:20][C:21]1[N:22]=[C:23]([CH3:30])[C:24]([C:28]#[N:29])=[C:25]([NH:19][C@H:17]([C:7]2[N:6]=[C:5]3[CH:4]=[CH:3][N:2]([CH3:1])[C:10]3=[CH:9][C:8]=2[CH:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[CH3:18])[N:26]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To a 10 mL vial were added (S)-1-(1-methyl-6-(tetrahydro-2H-pyran-4-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine (271 mg, 1.05 mmol), 2-amino-4-chloro-6-methylpyrimidine-5-carbonitrile (194 mg, 1.149 mmol) and Et3N (0.29 mL, 2.1 mmol) in DMF (5 mL). The resulting yellow solution was heated to 90° C. and stirred overnight. The product was purified by preparative HPLC eluting with 20-40% ACN in water (with 0.05% ammonium formate). The fractions containing the product were combined and lyophilized to give the title compound as a white solid (27 mg, 6.6%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.39-1.53 (m, 3 H), 1.58-1.86 (m, 3 H), 1.91-2.11 (m, 1 H), 2.18-2.29 (m, 3 H), 2.99-3.17 (m, 1 H), 3.37-3.61 (m, 2 H), 3.75-3.90 (m, 3 H), 3.90-4.10 (m, 2 H), 5.63-5.80 (m, 1 H), 6.44-6.57 (m, 1 H), 6.97-7.25 (m, 2 H), 7.32-7.45 (m, 1 H), 7.55-7.65 (m, 1 H), 7.83-7.97 (m, 1 H); ESI-MS m/z [M+H]+ calc'd for C21H25N2O, 392; found 392.

Workup

customThe product was purified by preparative HPLC
washeluting with 20-40% ACN in water (with 0.05% ammonium formate)
additionThe fractions containing the product

Sources & evidence

ORD record: ord-3ef11d76893a4fe7813d9ba201c21a0d
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08835420B2

Reaction notes

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