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

HRID 853883Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]([CH3:16])([CH3:15])[C:13]#[N:14])[C:6](=O)[C:5]12[O:22][CH2:21][CH2:20][CH2:19][O:18]1.N.C1COCC1>[Ni].CCO>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]3[CH2:11][C:12]([CH3:16])([CH3:15])[CH2:13][N:14]=[C:6]3[C:5]3([O:18][CH2:19][CH2:20][CH2:21][O:22]3)[C:4]=2[CH:3]=1

Participants

Conditions

Temperature: 135 °C

Procedure

A mixture of 3-(5′-chloro-2′-oxospiro[1,3-dioxane-2,3′-indol]-1′(2′H)-yl)-2,2-dimethylpropanenitrile (0.81 g, 2.53 mmol ), and wet Raney Nickel (0.88 g), in 2M EtOH.NH3 (60 mL) and THF (10 mL) was hydrogenated in a Parr Hydrogenation Bottle (500 mL) at 56 lb/in2 H2 for 17 hr. The Raney Nickel was removed by filtration through Sulka Floc and the filtrate was poured into a steel pressure vessel and heated at 135° C. for 22 hr. The reaction mixture was cooled to room temperature and concentrated. The crude product was purified on Biotage KP silica gel eluting with CH2Cl2/CH3OH/NH4OH, (97/2/1) to give the title compound as an off white solid (0.68 g, 88% yield). Anal. Calc'd for C16H19ClN2O2: C, 62.64; H, 6.24; N, 9.13. Found: C, 62.59; H, 6.19; N, 9.04. NMR (300 Mz, DMSO-d6): consistent; IR: consistent MS: (ES+) m/z 307 [M+H], one Cl pattern observed; m.p.: 121-122° C.

Workup

customfor 17 hr
customThe Raney Nickel was removed by filtration through Sulka Floc
additionthe filtrate was poured into a steel pressure vessel
temperatureThe reaction mixture was cooled to room temperature
concentrationconcentrated
customThe crude product was purified on Biotage KP silica gel eluting with CH2Cl2/CH3OH/NH4OH, (97/2/1)

Sources & evidence

ORD record: ord-f7a88949dc9a4603bbec2f0a4b8b665c
Source dataset: uspto-grants-2007_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07256198B2

Reaction notes

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