Hydrazine hydrate (1:1) → HCID 178527336, compound

HRID 1011604Notes

Reaction equation

HRID 1011604 reaction equation
[CH:1]1([C@H:4]2[C:8](=O)[CH2:7][CH:6]([CH:10]3[CH2:12][CH2:11]3)[N:5]2[S:13]([C:16]2[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=2)(=[O:15])=[O:14])[CH2:3][CH2:2]1.C[N:27]([CH:29](OC)OC)C.O.[NH2:35]N>>[CH:1]1([CH:4]2[C:8]3[C:7](=[N:35][NH:27][CH:29]=3)[C@H:6]([CH:10]3[CH2:12][CH2:11]3)[N:5]2[S:13]([C:16]2[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=2)(=[O:15])=[O:14])[CH2:3][CH2:2]1

Participants

4

Reactant 3

HCID 24654Hydrazine hydrate (1:1)HCID 78373Dimethylformamide dimethyl acetalHCID 57659766HCID 57659766, compound

Product 1

HCID 178527336HCID 178527336, compoundYield 19.4%

Procedure

(2S)-2,5-Dicyclopropyl-1-(4-(trifluoromethyl)phenylsulfonyl)pyrrolidin-3-one (21) (149 mg, 0.399 mmol) and DMF-DMA (0.059 mL, 0.439 mmol) where heated at 60° C. for 1.5 hr under nitrogen. The reaction was concentrated in vacuo and used directly in next step. This material was dissolved in ethanol (1.5 mL) and acetic acid (0.075 mL). Hydrazine hydrate (0.1 mL, 20.0 mmol) was added dropwise and the reaction stirred for 16 hr at rt. The reaction was concentrated in vacuo and the resulting crude product was purified by column chromatography using EtOAc/hexane gradients to yield (6S)-4,6-dicyclopropyl-5-(4-(trifluoromethyl)phenylsulfonyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole (22) (30.7 mg, 19.4% over two steps) as a white solid. 1H-NMR (CDCl3) δ 8.01 (d, 2H, J=8.2 Hz), 7.71 (d, 2H, J=8.2 Hz), 7.19 (s, 1H), 4.59 (d, 1H, J=10.3 Hz), 4.57 (d, 1H, J=10.3 Hz), 1.35 (m, 2H), 0.81 (m, 1H), 0.68-0.44 (m, 5H), (m, 1H), 0.31 (m, 1H), 0.19 (m, 1H); MS (m/z) 398.1 (M+H)+; retention time=7.168, method [7].

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. dissolutionThis material was dissolved in ethanol (1.5 mL)
  3. concentrationThe reaction was concentrated in vacuo
  4. customthe resulting crude product was purified by column chromatography

Sources & evidence

ORD record
ord-c208672e23914f82932c30dcf6853c2c
Source dataset
uspto-grants-2011_07
Patent number
US07977368B2

Reaction notes

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