Hydrochloric Acid → Mivavotinib

HRID 711565Notes

Reaction equation

C(OC([NH:8][C@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]1[NH:15][C:16]1[N:21]=[C:20]([C:22]2[CH:23]=[N:24][N:25]([CH3:27])[CH:26]=2)[C:19]2[C:28](=[O:38])[N:29](C(OC(C)(C)C)=O)[CH2:30][C:18]=2[C:17]=1[F:39])=O)(C)(C)C.Cl>CC(O)C>[NH2:8][C@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]1[NH:15][C:16]1[N:21]=[C:20]([C:22]2[CH:23]=[N:24][N:25]([CH3:27])[CH:26]=2)[C:19]2[C:28](=[O:38])[NH:29][CH2:30][C:18]=2[C:17]=1[F:39]

Participants

Conditions

Temperature: 65 °C

Procedure

A suspension of tert-butyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-7-fluoro-4-(1-methyl-1H-pyrazol-4-yl)-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate (2.148 g, 3.94 mmol) in IPA (21 mL) was heated to 70° C. at which point 2M HCl aq (9.86 mL, 19.72 mmol) was added. The reaction mixture was heated at 65° C. for approximately 3 h, cooled in an ice water bath for 1 h, and then filtered. The solids were rinsed with cold IPA (15 mL) and then dried in a 50° C. vacuum oven overnight to give an HCL salt of the title compound as a light yellow solid (1.404 g, 3.37 mmol) having 1.5-2 eq of associated water (by 1H NMR). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.46 (d, J=7.07 Hz, 2H), 1.57-1.76 (m, 3H), 1.76-2.04 (m, 3H), 3.31 (s, 3H), 3.67 (br s, 1H), 3.90 (s, 3H), 4.39 (d, J=2.53 Hz, 2H), 4.41-4.60 (m, 1H), 6.75 (d, J=6.57 Hz, 1H), 7.96 (br s, 3H), 8.22-8.31 (m, 1H), 8.34 (s, 1H), 8.84 (s, 1H). [M+H] calc'd for C17H21FN6O, 345. found 345.

Workup

additionwas added
temperaturecooled in an ice water bath for 1 h
filtrationfiltered
washThe solids were rinsed with cold IPA (15 mL)
customdried in a 50° C. vacuum oven overnight

Sources & evidence

ORD record: ord-1cea896a167c4b0b8ee48141e9accdec
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181255B2

Reaction notes

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