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

HRID 216081Notes

Reaction equation

[CH3:1][N:2]([CH3:27])[C:3](=[O:26])[O:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([NH:11][C:12]([C:14]2([CH2:20][C:21]3[N:22]=[CH:23][NH:24][CH:25]=3)[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)=[O:13])[CH:6]=1.Cl[C:29]1[C:30]2[C:37]([CH3:38])=[CH:36][NH:35][C:31]=2[N:32]=[CH:33][N:34]=1.C(N(CC)C(C)C)(C)C>C(O)(C)C>[CH3:27][N:2]([CH3:1])[C:3](=[O:26])[O:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([NH:11][C:12]([C:14]2([CH2:20][C:21]3[N:22]=[CH:23][NH:24][CH:25]=3)[CH2:19][CH2:18][N:17]([C:29]3[C:30]4[C:37]([CH3:38])=[CH:36][NH:35][C:31]=4[N:32]=[CH:33][N:34]=3)[CH2:16][CH2:15]2)=[O:13])[CH:6]=1

Participants

Conditions

Temperature: 100 °C

Procedure

3-(4-((1H-imidazol-4-yl)methyl)piperidine-4-carboxamido)phenyl dimethylcarbamate from step D (10 mg, 0.027 mmol), 4-chloro-5-methyl-7H-pyrrolo[2,3-d]pyrimidine (5 mg, 0.03 mmol), and N,N-diisopropylethylamine (23 μL, 0.135 mmol) were combined in isopropanol (0.5 mL). The resulting mixture was heated at 100° C. in a sealed pressure tube for 24 hours. The reaction mixture was cooled and concentrated under vacuum. The residue was purified by prep HPLC (10-95% MeOH:H2O with 0.1% HCOOH), then treated with AcOH in H2O and lyophilized to give the title compound (5.7 mg, 42%) as the acetate salt.

Workup

temperatureThe reaction mixture was cooled
concentrationconcentrated under vacuum
customThe residue was purified by prep HPLC (10-95% MeOH:H2O with 0.1% HCOOH)
additiontreated with AcOH in H2O

Sources & evidence

ORD record: ord-70fc28b1c15f440c92e0fb3aefb7cd32
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08193202B2

Reaction notes

Loading…