Cyclobutanecarbonyl chloride → HCID 59352522, compound

HRID 1965774Notes

Reaction equation

HRID 1965774 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]1([C:24]3[C:15](=[CH:16][C:17]4[O:22][CH2:21][CH2:20][O:19][C:18]=4[CH:23]=3)[O:14][CH2:13]1)[C:5](=[O:12])[N:6]2[CH3:11].[CH:25]1([C:29](Cl)=[O:30])[CH2:28][CH2:27][CH2:26]1>ClCCl.N1C=CC=CC=1>[CH3:11][N:6]1[C:7]2[C:3](=[C:2]([NH:1][C:29]([CH:25]3[CH2:28][CH2:27][CH2:26]3)=[O:30])[CH:10]=[CH:9][CH:8]=2)[C:4]2([C:24]3[C:15](=[CH:16][C:17]4[O:22][CH2:21][CH2:20][O:19][C:18]=4[CH:23]=3)[O:14][CH2:13]2)[C:5]1=[O:12]

Participants

5

Reactant 2

HCID 78705Cyclobutanecarbonyl chlorideHCID 59352092HCID 59352092, compound

Product 1

HCID 59352522HCID 59352522, compoundYield 83.1%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 4′-amino-1′-methyl-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (700 mg, 1.72 mmol) in dichloromethane (50 mL) and pyridine (5 mL) was added cyclobutanecarbonyl chloride (0.17 mL, 1.48 mmol) at 0° C. The reaction mixture was stirred at ambient temperature for 18 h, diluted with dichloromethane (150 mL), washed sequentially with water, 10% w/v hydrochloric acid, water and brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was subjected to column chromatography and eluted with ethyl acetate/hexanes (1/3) to afford N-(1′-methyl-2′-oxo-1′,2,2′,3-tetrahydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-4′-yl)cyclobutanecarboxamide (0.50 g, 71%): mp 234-236° C. (ethyl acetate/hexanes); 1H NMR (300 MHz, DMSO-d6) δ 8.15 (s, 1H), 7.32-7.26 (m, 1H), 7.11-7.08 (m, 1H), 6.94-6.91 (m, 1H), 6.43 (s, 1H), 6.17 (s, 1H), 4.68 (ABq, 2H), 4.13-4.05 (m, 4H), 3.15 (s, 3H), 2.96-2.90 (m, 1H), 2.05-1.64 (m, 6H); 13C NMR (75 MHz, DMSO-d6) δ 176.6, 173.5, 155.1, 144.6, 144.3, 138.3, 134.6, 129.5, 125.3, 120.8, 119.4, 112.0, 106.8, 98.8, 78.2, 64.6, 64.0, 57.1, 27.1, 25.0, 24.9, 17.9; MS (ES+) m/z 406.9 (M+1).

Workup

  1. washwashed sequentially with water, 10%
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated in vacuo
  5. washeluted with ethyl acetate/hexanes (1/3)

Sources & evidence

ORD record
ord-087fa3bcef014a879003f190e173316d
Source dataset
uspto-grants-2013_04
Patent number
US08415370B2

Reaction notes

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