Triethylamine → 1-(5-(1-((2,6-Diamino-5-chloropyrimidin-4-yl)amino)ethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)azetidin-3-ol

HRID 75340Notes

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].[Cl:19][C:20]1[C:21]([NH2:28])=[N:22][C:23]([NH2:27])=[N:24][C:25]=1Cl.CCN(CC)CC>C(#N)C.O>[NH2:27][C:23]1[N:24]=[C:25]([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])[C:20]([Cl:19])=[C:21]([NH2:28])[N:22]=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), 5,6-dichloropyrimidine-2,4-diamine (65.4 mg, 0.365 mmol) and Et3N (0.085 mL, 0.61 mmol) in acetonitrile (2 mL) and water (0.5 mL). The resulting brown 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 an off-white solid (10 mg, 8.5%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.03-1.14 (m, 3 H), 1.28-1.37 (m, 3 H), 3.48-3.56 (m, 1 H), 3.65-3.74 (m, 1 H), 3.74-3.83 (m, 3 H), 4.02-4.15 (m, 1 H), 4.23-4.33 (m, 1 H), 4.51-4.61 (m, 1 H), 5.33-5.48 (m, 1 H), 5.56-5.63 (m, 1 H), 5.64-5.73 (m, 2 H), 5.86-6.00 (m, 2H), 6.40-6.52 (m, 2 H), 7.07-7.16 (m, 1 H), 7.35-7.46 (m, 1 H); ESI-MS m/z [M+H]+ calc'd for C17H21ClN8O, 389; found 389.

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-a942a7b007ce48f8bbc5543096185225
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08835420B2

Reaction notes

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