Dimethylamine → HCID 178483299, compound

HRID 1053625Notes

Reaction equation

[CH3:1][NH:2][CH3:3].[CH2:4]=O.[NH:6]1[C:14]2[C:9](=[C:10]([CH2:15][N:16]([CH2:25][CH:26]3[CH2:29][CH2:28][CH2:27]3)[C:17]([C:19]3[NH:23][N:22]=[C:21]([Cl:24])[CH:20]=3)=[O:18])[CH:11]=[CH:12][CH:13]=2)[CH:8]=[CH:7]1>CC(O)=O.CCOC(C)=O>[Cl:24][C:21]1[CH:20]=[C:19]([C:17]([N:16]([CH2:25][CH:26]2[CH2:27][CH2:28][CH2:29]2)[CH2:15][C:10]2[CH:11]=[CH:12][CH:13]=[C:14]3[C:9]=2[C:8]([CH2:1][N:2]([CH3:4])[CH3:3])=[CH:7][NH:6]3)=[O:18])[NH:23][N:22]=1

Participants

Conditions

Temperature: 75 °C

Procedure

To a solution of dimethyl amine (109 uL of 2 molar, 0.218 mmol) in AcOH (1 mL) was added formaldehyde (7.91 uL of 38% aqueous, 0.109 mmol). After stirring for 15 min a solution of N-((1H-indol-4-yl)methyl)-3-chloro-N-(cyclobutylmethyl)-1H-pyrazole-5-carboxamide (34 mg, 0.099 mmol) in acetic acid (1 mL) was added. The reaction was stirred overnight at 75° C. then cooled to room temperature and diluted with EtOAc (3 mL) and washed with saturated potassium carbonate solution (3 mL) twice and water (2 mL) once. The organic layer was then stripped in vacuo and the product purified by normal phase chromatography (DCM/MeOH, 0→20%). After isolation of the product the purity was not high enough so it was repurified by semi prep HPLC (ACN/Water+0.05% TFA) to give the desired product in 97% purity.

Workup

additionwas added
temperaturethen cooled to room temperature
washwashed with saturated potassium carbonate solution (3 mL) twice
customthe product purified by normal phase chromatography (DCM/MeOH, 0→20%)
customwas repurified by semi prep HPLC (ACN/Water+0.05% TFA)

Sources & evidence

ORD record: ord-19dec2836c004b1aa759b6a881505e4b
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394257B2

Reaction notes

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