Diisopropylethylamine → 3-(4-(2-(dimethylamino)ethyl)-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamido)phenyl dimethylcarbamate

HRID 216076Notes

Reaction equation

[CH3:1][N:2]([CH3:26])[C:3](=[O:25])[O:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([NH:11][C:12]([C:14]2([CH2:20][CH2:21][N:22]([CH3:24])[CH3:23])[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)=[O:13])[CH:6]=1.Cl[C:28]1[C:29]2[C:36]([CH3:37])=[CH:35][NH:34][C:30]=2[N:31]=[CH:32][N:33]=1.C(N(CC)C(C)C)(C)C>C(O)C(C)C>[CH3:26][N:2]([CH3:1])[C:3](=[O:25])[O:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([NH:11][C:12]([C:14]2([CH2:20][CH2:21][N:22]([CH3:24])[CH3:23])[CH2:19][CH2:18][N:17]([C:28]3[C:29]4[C:36]([CH3:37])=[CH:35][NH:34][C:30]=4[N:31]=[CH:32][N:33]=3)[CH2:16][CH2:15]2)=[O:13])[CH:6]=1

Participants

Conditions

Temperature: 110 °C

Procedure

Impure 3-(4-(2-(dimethylamino)ethyl)piperidine-4-carboxamido)phenyl dimethylcarbamate from step D (173 mg) was combined with 4-chloro-5-methyl-7H-pyrrolo[2,3-d]pyrimidine (50 mg, 0.30 mmol) and N,N-diisopropylethylamine (0.174 mL, 5 mmol) in isobutanol (0.4 mL) and heated at 110° C. for 7 hours. The reaction was cooled to room temperature and concentrated under vacuum. The residue was purified by prep HPLC (30×100 mm C18 column, 10-70% MeCN:H2O (10 mM NH4OAc), 12 min, 45 mL/min) and lyophilized to give the title compound (60 mg) as the di-acetate salt.

Workup

temperatureThe reaction was cooled to room temperature
concentrationconcentrated under vacuum
customThe residue was purified by prep HPLC (30×100 mm C18 column, 10-70% MeCN:H2O (10 mM NH4OAc), 12 min, 45 mL/min)

Sources & evidence

ORD record: ord-45a5ecbd63f64afaad0cfd355d15d5de
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08193202B2

Reaction notes

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