Ammonia → 3',3'-dimethyl-8'-(pyrrolidin-1-ylsulfonyl)-3',4'-dihydro-2'H-spiro[1,3-dioxane-2,10'-pyrimido[1,2-a]indole]

HRID 853876Notes

Reaction equation

[CH3:1][C:2]([CH3:29])([CH2:5][N:6]1[C:14]2[C:9](=[CH:10][C:11]([S:15]([N:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)(=[O:17])=[O:16])=[CH:12][CH:13]=2)[C:8]2([O:27][CH2:26][CH2:25][CH2:24][O:23]2)[C:7]1=O)[C:3]#[N:4].N.C1COCC1.[H][H]>[Ni].CCO>[CH3:1][C:2]1([CH3:29])[CH2:5][N:6]2[C:14]3[CH:13]=[CH:12][C:11]([S:15]([N:18]4[CH2:19][CH2:20][CH2:21][CH2:22]4)(=[O:16])=[O:17])=[CH:10][C:9]=3[C:8]3([O:27][CH2:26][CH2:25][CH2:24][O:23]3)[C:7]2=[N:4][CH2:3]1

Participants

Conditions

Temperature: 135 °C

Procedure

A mixture of 2,2-dimethyl-3-[2′-oxo-5′-(pyrrolidin-1-ylsulfonyl)spiro[1,3-dioxane-2,3′-indol]-1′(2′H)-yl]propanenitrile (0.69 g, 1.64 mmol) and wet Raney Nickel (0.70 g) in 2M EtOH.NH3 (50 mL) and THF (20 mL) was hydrogenated in a Parr hydrogenation bottle (500 mL) at 541 b/in2 hydrogen for 67 hr. The Raney Nickel was removed by filtration through Sulka Floc and the filtrate was poured into a steel pressure vessel, diluted with 2M EtOH.NH3 (50 mL) and THF (20 mL) and heated at 135° C. for 22 hr. The reaction was cooled to room temperature and concentrated. The crude product was purified on Biotage KP silica gel eluting with CH2Cl2/CH3OH/NH4OH (98.5/1/.05) to give the title compound as a white solid (0.300 g, 45% yield). NMR: consistent. MS: (API-ES+) m/z 406 [M+H].

Workup

customThe Raney Nickel was removed by filtration through Sulka Floc
additionthe filtrate was poured into a steel pressure vessel
additiondiluted with 2M EtOH
temperatureThe reaction was cooled to room temperature
concentrationconcentrated
customThe crude product was purified on Biotage KP silica gel eluting with CH2Cl2/CH3OH/NH4OH (98.5/1/.05)

Sources & evidence

ORD record: ord-7a0930446c61405f8e08ea62b19dc3c6
Source dataset: uspto-grants-2007_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07256198B2

Reaction notes

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