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

HRID 75329Notes

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]([NH2:27])[C:24]([C:28]#[N:29])=[C:23](Cl)[N:22]=1.CCN(CC)CC>CN(C=O)C>[NH2:20][C:21]1[N:26]=[C:25]([NH2:27])[C:24]([C:28]#[N:29])=[C:23]([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:22]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To a 20 mL vial were added (S)-1-(1-methyl-6-(tetrahydro-2H-pyran-4-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine (336 mg, 1.296 mmol), 2,4-diamino-6-chloropyrimidine-5-carbonitrile (242 mg, 1.425 mmol) and Et3N (1.8 mL, 13 mmol) in DMF (7 mL). The resulting yellow solution was heated to 90° C. and stirred overnight. The crude product was purified by preparative HPLC eluting with 25-50% ACN in water (with 0.05% ammonium bicarbonate). The fractions containing the desired product were combined and lyophilized to give the title compound as a white solid (147 mg, 28%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.37-1.51 (m, 3 H), 1.58-1.87 (m, 3 H), 1.91-2.07 (m, 1 H), 3.04-3.18 (m, 1 H), 3.43-3.60 (m, 3 H), 3.77-3.88 (m, 3 H), 3.90-4.08 (m, 2 H), 5.64-5.80 (m, 1H), 6.39-6.54 (m, 3 H), 6.56-6.67 (m, 2 H), 6.82-6.96 (m, 1 H), 7.54-7.66 (m, 1 H), 7.81-7.96 (m, 1 H),); ESI-MS m/z [M+H]+ calc'd for C20H24N8O, 393; found 393.

Workup

customThe crude product was purified by preparative HPLC
washeluting with 25-50% ACN in water (with 0.05% ammonium bicarbonate)
additionThe fractions containing the desired product

Sources & evidence

ORD record: ord-6cac50e4189d4987abe2a7e5afc0f5aa
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08835420B2

Reaction notes

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