Hydrochloric Acid → HCID 118114860, compound

HRID 1050622Notes

Reaction equation

[C:1]([C:3]1[N:4]=[CH:5][C:6]([NH:16][C@@H:17]2[CH2:23][CH2:22][CH2:21][CH2:20][N:19]([C:24]([N:26]([CH3:28])[CH3:27])=[O:25])[CH2:18]2)=[N:7][C:8]=1[NH:9][C:10]1[S:14][N:13]=[C:12]([CH3:15])[CH:11]=1)#[N:2].Cl.CC#N.C(O)(C(F)(F)F)=[O:34]>OS(O)(=O)=O.O.CO>[C:1]([C:3]1[N:4]=[CH:5][C:6]([NH:16][C@@H:17]2[CH2:23][CH2:22][CH2:21][CH2:20][N:19]([C:24]([N:26]([CH3:27])[CH3:28])=[O:25])[CH2:18]2)=[N:7][C:8]=1[NH:9][C:10]1[S:14][N:13]=[C:12]([CH3:15])[CH:11]=1)(=[O:34])[NH2:2]

Participants

Conditions

Temperature: 80 °C

Procedure

(R)-3-(5-Cyano-6-(3-methylisothiazol-5-ylamino)pyrazin-2-ylamino)-N,N-dimethylazepane-1-carboxamide (510) (20 mg, 0.050 mmol) was dissolved in 5 mL TFA, and the solution was heated to 80° C. Concentrated H2SO4 (7 drops) was added dropwise, and the reaction was allowed to stir for 30 min Additional H2SO4 (15 drops) was added dropwise and the reaction was allowed to stir for 30 minutes. The reaction was cooled to RT, and diluted with 2 mL water and 2 mL methanol. The mixture was then directly subjected to reverse phase preparative HPLC using 5 mM HCl (aq) and neat MeCN as mobile phases, and lyophilized to give (R)-3-(5-carbamoyl-6-(3-methylisothiazol-5-ylamino)pyrazin-2-ylamino)-N,N-dimethylazepane-1-carboxamide (511) (16 mg, 0.038 mmol, 76% yield). LC-MS (ESI): m/z (M+1) 419.6. Proton NMR (DMSO-d6): δ 12.27 (1H, s), 8.05 (1H, s), 7.81 (1H, s), 7.48-7.44 (2H, m), 6.85 (1H, s), 4.46 (1H, m), 3.35 (4H, m), 2.70 (6H, s), 2.30 (3H, s), 2.02 (1H, m), 1.79 (2H, m), 1.70 (1H, m), 1.57 (2H, m) ppm.

Workup

additionwas added dropwise
temperatureThe reaction was cooled to RT

Sources & evidence

ORD record: ord-5056ec86b52e47e296f6d5b89f4ce436
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09382246B2

Reaction notes

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