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

HRID 75324Notes

Reaction equation

[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([NH:10][C@H:11]([C:13]2[N:18]=[C:17]3[CH:19]=[CH:20][N:21]([CH3:22])[C:16]3=[CH:15][C:14]=2[C:23]2[N:24]=[CH:25][S:26][CH:27]=2)[CH3:12])[N:5]=[C:4](S(C)(=O)=O)[N:3]=1.[NH3:32]>O1CCOCC1>[NH2:32][C:4]1[N:3]=[C:2]([NH2:1])[C:7]([C:8]#[N:9])=[C:6]([NH:10][C@H:11]([C:13]2[N:18]=[C:17]3[CH:19]=[CH:20][N:21]([CH3:22])[C:16]3=[CH:15][C:14]=2[C:23]2[N:24]=[CH:25][S:26][CH:27]=2)[CH3:12])[N:5]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a sealed tube were added (S)-4-amino-6-((1-(1-methyl-6-(thiazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)amino)-2-(methylsulfonyl)pyrimidine-5-carbonitrile (20 mg, 0.044 mmol) in dioxane (5 mL) along with 0.5M ammonia in dioxane (0.440 mL, 0.220 mmol). The reaction mixture was heated at 60° C. overnight and then concentrated. The crude product was taken up in DMF and purified by preparative HPLC (basic mode) eluting with 30-40% ACN in water. The fractions containing the desired product were combined and concentrated in vacuo to give the title compound as an off-white solid (12 mg, 70%). 1H NMR (500 MHz, CD3OD) δ ppm 1.42 (d, J=6.83 Hz, 3 H), 3.87 (s, 3 H), 5.76 (d, J=6.83 Hz, 1 H), 6.60-6.67 (m, 1 H), 7.56 (s, 1 H), 7.76 (s, 1 H), 7.91 (d, J=0.98 Hz, 1 H), 9.16 (d, J=1.95 Hz, 1 H); ESI-MS m/z [M+H]+ calc'd for C18H17N9S, 392; found 392.

Workup

concentrationconcentrated
custompurified by preparative HPLC (basic mode)
washeluting with 30-40% ACN in water
additionThe fractions containing the desired product
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-028fa047a0e147c68f4a6c255b11b565
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08835420B2

Reaction notes

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