Diisopropylethylamine → N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-((6-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[3,2-b]pyridin-5-yl)methyl)-N2-methylpyrimidine-2,4-diamine

HRID 2409077Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]2[N:13]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[CH:12]=[CH:11][C:5]2=[N:6][C:7]=1[CH2:8][NH:9][CH3:10].Cl[C:23]1[N:28]=[C:27]([NH:29][C:30]2[CH:34]=[C:33]([CH:35]3[CH2:37][CH2:36]3)[NH:32][N:31]=2)[CH:26]=[CH:25][N:24]=1.CCN(C(C)C)C(C)C>CC(C(O)C(C)C)C>[CH:35]1([C:33]2[NH:32][N:31]=[C:30]([NH:29][C:27]3[CH:26]=[CH:25][N:24]=[C:23]([N:9]([CH2:8][C:7]4[N:6]=[C:5]5[CH:11]=[CH:12][N:13]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[C:4]5=[CH:3][C:2]=4[F:1])[CH3:10])[N:28]=3)[CH:34]=2)[CH2:37][CH2:36]1

Participants

Conditions

Temperature: 135 °C

Procedure

A mixture of (6-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-N-methylmethanamine (50 mg, 0.17 mmol), 2-chloro-N-(5-cyclopropyl-1H-pyrazol-3-yl)pyrimidin-4-amine (38 mg, 0.17 mmol), and DIPEA (66 mg, 0.51 mmol) in 2,4-dimethylpentan-3-ol (2 mL) was heated at 135° C. for 15 h. The reaction mixture was concentrated under reduced pressure. The residue was purified by SiO2 chromatography eluting with DCM/MeOH (10:1) to afford 40 mg (30%) of N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-((6-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[3,2-b]pyridin-5-yl)methyl)-N2-methylpyrimidine-2,4-diamine as a brown oil (40 mg, 30%). MS (ESI): m/z=509.4 [M+H]+.

Workup

concentrationThe reaction mixture was concentrated under reduced pressure
customThe residue was purified by SiO2 chromatography
washeluting with DCM/MeOH (10:1)

Sources & evidence

ORD record: ord-c93c3234eaf04fa5b0b001b988c9c02c
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08815877B2

Reaction notes

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