Dimethylformamide → 1-(Benzo[d][1,3]dioxol-5-yl)-N-(2-tert-butyl-1H-indol-5-yl)cyclopropanecarboxamide

HRID 468423Notes

Reaction equation

HRID 468423 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([OH:15])=O)[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1.CN(C)C=O.[C:21]([C:25]1[NH:26][C:27]2[C:32]([CH:33]=1)=[CH:31][C:30]([NH2:34])=[CH:29][CH:28]=2)([CH3:24])([CH3:23])[CH3:22].C(N(CC)CC)C>S(Cl)(Cl)=O.ClCCl>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:34][C:30]4[CH:31]=[C:32]5[C:27](=[CH:28][CH:29]=4)[NH:26][C:25]([C:21]([CH3:24])([CH3:23])[CH3:22])=[CH:33]5)=[O:15])[CH2:11][CH2:12]3)=[CH:9][C:4]=2[O:3][CH2:2]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 27609662-tert-butyl-1H-indol-5-amineHCID 143496081-(1,3-Dioxaindan-5-yl)cyclopropane-1-carboxylic acid

Product 1

HCID 247629031-(Benzo[d][1,3]dioxol-5-yl)-N-(2-tert-butyl-1H-indol-5-yl)cyclopropanecarboxamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 24386Thionyl ChlorideSolvent

Procedure

1-Benzo[1,3]dioxol-5-yl-cyclopropanecarboxylic acid (1.09 g, 5.30 mmol) was dissolved in 2 mL of thionyl chloride under nitrogen. A catalytic amount (0.3 mL) of N,N-dimethylformamide (DMF) was added and the reaction mixture was stirred for 30 minutes. The excess thionyl chloride was evaporated and the resulting residue was dissolved in 15 mL of dichloromethane. This solution was slowly added to a solution of 2-tert-butyl-1H-indol-5-amine (1.0 g, 5.3 mmol) in 10 mL of dichloromethane containing triethylamine (1.69 mL, 12.1 mmol). The resulting solution was allowed to stir for 10 minutes. The solvent was evaporated to dryness and the crude reaction mixture was purified by silica gel column chromatography using a gradient of 5-50% ethyl acetate in hexanes. The pure fractions were combined and evaporated to dryness to yield a pale pink powder (1.24 g 62%). ESI-MS calc. 376.18, found 377.3 (M+1)+. Retention time of 3.47 minutes. 1H NMR (400 MHz, DMSO) δ 10.77 (s, 1H), 8.39 (s, 1H), 7.56 (d, J=1.4 Hz, 1H), 7.15 (d, J=8.6 Hz, 1H), 7.05-6.87 (m, 4H), 6.03 (s, 3H), 1.44-1.37 (m, 2H), 1.33 (s, 9H), 1.05-1.00 (m, 2H).

Workup

  1. customThe excess thionyl chloride was evaporated
  2. dissolutionthe resulting residue was dissolved in 15 mL of dichloromethane
  3. stirringto stir for 10 minutes
  4. customThe solvent was evaporated to dryness
  5. customthe crude reaction mixture
  6. customwas purified by silica gel column chromatography
  7. customevaporated to dryness
  8. customto yield a pale pink powder (1.24 g 62%)

Sources & evidence

ORD record
ord-26bf6c1504b44a578a499f1f7d924095
Source dataset
uspto-grants-2014_01
Patent number
US08623905B2

Reaction notes

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