HCID 67447598, compound → HCID 178520034, compound

HRID 1466345Notes

Reaction equation

HRID 1466345 reaction equation
[O:1]=[C:2]1[C@@:10]2([CH2:12][C@H:11]2[C:13]2[CH:21]=[C:20]3[C:16]([C:17]([C:22]#N)=[N:18][NH:19]3)=[CH:15][CH:14]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[NH:3]1.[PH2]([O-])=[O:25].[Na+]>N1C=CC=CC=1.O.[Ni]>[O:1]=[C:2]1[C@@:10]2([CH2:12][C@H:11]2[C:13]2[CH:21]=[C:20]3[C:16]([C:17]([CH:22]=[O:25])=[N:18][NH:19]3)=[CH:15][CH:14]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[NH:3]1

Participants

6

Reactant 2

HCID 67447598HCID 67447598, compoundHCID 178527019HCID 178527019, compound

Product 1

HCID 178520034HCID 178520034, compoundYield 30%

Reagents, catalysts & solvents 3

HCID 935NickelCatalystHCID 962WaterSolvent2×HCID 1049PyridineSolvent

Procedure

To a solution of 6-((1R*,2S*)-2′-oxospiro[cyclopropane-1,3′-indoline]-2-yl)-1H-indazole-3-carbonitrile (1 g, 3.3 mmol) in pyridine (30 mL) acetic acid (8 mL) and water (8 mL) and Raney Nickel (1 g). Sodium hypophosphite (1.8 g, 21 mmol) was dissolved in water (10 mL) and added dropwise and the reaction was stirred overnight. The product was extracted into ethyl acetate (300 mL), washed with brine (50 mL), dried over MgSO4 and concentrated to dryness. The residue was purified by silica gel chromatography (95:5 CH2Cl2/MeOH) to give the title compound as a yellow solid (300 mg, 30%). 1H NMR (400 MHz, CD3OD) δ 10.17 (s, 1H), 8.10 (d, J=8.3 Hz, 1H), 7.55 (s, 1H), 7.17 (d, J=8.5 Hz, 1H) 7.08-7.04 (m, 1H), 6.94 (d, J=8.3 Hz, 1H), 6.56 (t, J=7.6 Hz, 1H), 5.93 (d, J=7.5 Hz, 1H), 3.38-3.34 (m, 1H), 2.27-2.17 (m, 1H).

Workup

  1. additionadded dropwise
  2. extractionThe product was extracted into ethyl acetate (300 mL)
  3. washwashed with brine (50 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated to dryness
  6. customThe residue was purified by silica gel chromatography (95:5 CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-b77a62c4a38a47a5a669a8ef82d0fb91
Source dataset
uspto-grants-2015_04
Patent number
US08999968B2

Reaction notes

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