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

HRID 75339Notes

Reaction equation

[NH2:1][CH:2]([C:4]1[N:9]=[C:8]2[CH:10]=[CH:11][N:12]([CH3:13])[C:7]2=[CH:6][C:5]=1[N:14]1[CH2:17][CH:16]([OH:18])[CH2:15]1)[CH3:3].[NH2:19][C:20]1[N:25]=[C:24]([NH2:26])[C:23]([C:27]#[N:28])=[C:22](Cl)[N:21]=1.CCN(CC)CC>C(#N)C>[NH2:19][C:20]1[N:25]=[C:24]([NH2:26])[C:23]([C:27]#[N:28])=[C:22]([NH:1][CH:2]([C:4]2[N:9]=[C:8]3[CH:10]=[CH:11][N:12]([CH3:13])[C:7]3=[CH:6][C:5]=2[N:14]2[CH2:17][CH:16]([OH:18])[CH2:15]2)[CH3:3])[N:21]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To a 10 mL vial were added 1-(5-(1-aminoethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)azetidin-3-ol (75 mg, 0.304 mmol), 2,4-diamino-6-chloropyrimidine-5-carbonitrile (62.0 mg, 0.365 mmol) and Et3N (0.085 mL, 0.61 mmol) in acetonitrile (2 mL). The resulting yellow solution was heated to 90° C. and stirred overnight. The crude product was purified by preparative HPLC eluting with 20-40% 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 pale yellow solid (5 mg, 5%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.30-1.40 (m, 4 H), 3.47-3.58 (m, 1 H), 3.67-3.75 (m, 1 H), 3.75-3.80 (m, 4 H), 4.05-4.14 (m, 1 H), 4.20-4.33 (m, 1 H), 4.51-4.63 (m, 1 H), 5.40-5.53 (m, 1H), 5.57-5.68 (m, 1 H), 6.38-6.53 (m, 3 H), 6.54-6.66 (m, 2 H), 6.76-6.86 (m, 1 H), 7.10-7.20 (m, 1 H), 7.36-7.46 (m, 1 H); ESI-MS m/z [M+H]+ calc'd for C18H21N9O, 380; found 380.

Workup

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

Sources & evidence

ORD record: ord-6d8b8aecf5404bc895670e899f3bc35e
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08835420B2

Reaction notes

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