Ammonia → 8-{[(2S)-2-(Hydroxymethyl)pyrrolidin-1-yl]sulfonyl}-3,3-dimethyl-3,4-dihydropyrimido[1,2-a]indol-10(2H)-one

HRID 853864Notes

Reaction equation

C([O:8][CH2:9][C@@H:10]1[CH2:14][CH2:13][CH2:12][N:11]1[S:15]([C:18]1[CH:19]=[C:20]2[C:24](=[CH:25][CH:26]=1)[N:23]([CH2:27][C:28]([CH3:32])([CH3:31])[C:29]#[N:30])[C:22](=O)[C:21]12OCCC[O:34]1)(=[O:17])=[O:16])C1C=CC=CC=1.N.C1COCC1>[Ni].CCO>[OH:8][CH2:9][C@@H:10]1[CH2:14][CH2:13][CH2:12][N:11]1[S:15]([C:18]1[CH:26]=[CH:25][C:24]2[N:23]3[CH2:27][C:28]([CH3:32])([CH3:31])[CH2:29][N:30]=[C:22]3[C:21](=[O:34])[C:20]=2[CH:19]=1)(=[O:17])=[O:16]

Participants

Conditions

Temperature: 132 °C

Procedure

A mixture of 3-[5′-({(2S)-2-[(benzyloxy)methyl]pyrrolidin-1-yl}sulfonyl)-2′-oxospiro[1,3-dioxane-2,3′-indol]-1′(2′H)-yl]-2,2-dimethylpropanenitrile (3.00 g, 5.56 mmol), wet Raney Nickel (3.18 g) in 2M EtOH.NH3 (180 mL) and THF (30 mL) was hydrogenated at 54 lb/in2 H2 for 22 hr. The reaction was filtered through Sulka Floc and the filtrate was poured into a steel pressure vessel and heated to 132° C. for 18 hr. After cooling to room temperature the reaction was concentrated. The crude product was purified on Biotage KP silica gel eluting with CH2Cl2/CH3OH/NH4OH (98.5/1/0.5) to give the title compound as a white solid (1.77 g, 60% ). NMR (400 MHz, DMSO-d6): consistent.

Workup

customfor 22 hr
filtrationThe reaction was filtered through Sulka Floc
additionthe filtrate was poured into a steel pressure vessel
temperatureAfter cooling to room temperature the reaction
concentrationwas concentrated
customThe crude product was purified on Biotage KP silica gel eluting with CH2Cl2/CH3OH/NH4OH (98.5/1/0.5)

Sources & evidence

ORD record: ord-ba46ce6c6b79402d9a8286788b7fd429
Source dataset: uspto-grants-2007_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07256198B2

Reaction notes

Loading…