Formaldehyde → 6'-(3-cyclopropyl-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)-3H-imidazo[4,5-c]pyridin-6-yl)-1,1'-dimethylspiro[azetidine-3,3'-indolin]-2'-one

HRID 2209161Notes

Reaction equation

HRID 2209161 reaction equation
C=O.[CH:3]1([N:6]2[C:10]3[C:11]([O:29][C@@H:30]([C@@H:32]4[CH2:36][C:35](=[O:37])[NH:34][CH2:33]4)[CH3:31])=[N:12][C:13]([C:15]4[CH:23]=[C:22]5[C:18]([C:19]6([CH2:28][NH:27][CH2:26]6)[C:20](=[O:25])[N:21]5[CH3:24])=[CH:17][CH:16]=4)=[CH:14][C:9]=3[N:8]=[CH:7]2)[CH2:5][CH2:4]1.[C:38](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.O.C(OCC)(=O)C>[CH:3]1([N:6]2[C:10]3[C:11]([O:29][C@@H:30]([C@@H:32]4[CH2:36][C:35](=[O:37])[NH:34][CH2:33]4)[CH3:31])=[N:12][C:13]([C:15]4[CH:23]=[C:22]5[C:18]([C:19]6([CH2:26][N:27]([CH3:38])[CH2:28]6)[C:20](=[O:25])[N:21]5[CH3:24])=[CH:17][CH:16]=4)=[CH:14][C:9]=3[N:8]=[CH:7]2)[CH2:5][CH2:4]1

Participants

7

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 1178437396'-(3-cyclopropyl-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)-3H-imidazo[4,5-c]pyridin-6-yl)-1'-methylspiro[azetidine-3,3'-indolin]-2'-one

Product 1

HCID 1178427886'-(3-cyclopropyl-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)-3H-imidazo[4,5-c]pyridin-6-yl)-1,1'-dimethylspiro[azetidine-3,3'-indolin]-2'-one

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Formaldehyde in water (37%, 0.07 mL, 0.89 mmol) was added to a mixture of 6′-(3-cyclopropyl-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)-3H-imidazo[4,5-c]pyridin-6-yl)-1′-methylspiro[azetidine-3,3′-indolin]-2′-one 3.85 (42 mg, 0.089 mmol) in 1,2-dichloroethane (1.5 mL). After 15 min, sodium triacetoxyborohydride (78 mg, 0.37 mmol) was added and mixture stirred at room temperature overnight. The reaction mixture was then diluted with water and ethyl acetate. The phases were separated, and the aqueous phase was extracted with ethyl acetate. The combined organic phase was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified via silica gel column chromatography (0-20% methanol in dichloromethane) to afford 6′-(3-cyclopropyl-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)-3H-imidazo[4,5-c]pyridin-6-yl)-1,1′-dimethylspiro[azetidine-3,3′-indolin]-2′-one 3.86.

Workup

  1. customThe phases were separated
  2. extractionthe aqueous phase was extracted with ethyl acetate
  3. dry with materialThe combined organic phase was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified via silica gel column chromatography (0-20% methanol in dichloromethane)

Sources & evidence

ORD record
ord-a58535e5bfd64fa1b0c0685f9066eb66
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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