Dimethylformamide → HCID 16752708, compound

HRID 1847491Notes

Reaction equation

HRID 1847491 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(N(CC)CC)C.[NH2:28][C:29]1[CH:30]=[C:31]2[C:35](=[CH:36][CH:37]=1)[NH:34][C:33]([C:38]([O:40][CH2:41][CH3:42])=[O:39])=[CH:32]2>S(Cl)(Cl)=O.ClCCl>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:28][C:29]4[CH:30]=[C:31]5[C:35](=[CH:36][CH:37]=4)[NH:34][C:33]([C:38]([O:40][CH2:41][CH3:42])=[O:39])=[CH:32]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 10726872Ethyl 5-amino-1H-indole-2-carboxylateHCID 143496081-(1,3-Dioxaindan-5-yl)cyclopropane-1-carboxylic acid

Product 1

HCID 16752708HCID 16752708, compoundYield 88%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 24386Thionyl ChlorideSolvent

Procedure

1-Benzo[1,3]dioxol-5-yl-cyclopropanecarboxylic acid (2.07 g, 10.0 mmol) was dissolved in thionyl chloride (2.2 mL) under N2. N,N-dimethylformamide (0.3 mL) was added and the solution was allowed to stir for 30 minutes. The excess thionyl chloride was removed under vacuum and the resulting solid was dissolved in anhydrous dichloromethane (15 mL) containing triethylamine (2.8 mL, 20.0 mmol). Ethyl 5-amino-1H-indole-2-carboxylate (2.04 g, 10.0 mmol) in 15 mL of anhydrous dichloromethane was slowly added to the reaction. The resulting solution was allowed to stir for 1 hour. The reaction mixture was diluted to 50 mL with dichloromethane and washed three times with 50 mL of 1N HCl, saturated aqueous sodium bicarbonate, and saturated aqueous sodium chloride. The organic layer was dried over sodium sulfate and evaporated to dryness to yield ethyl 5-(1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-1H-indole-2-carboxylate as a gray solid (3.44 g, 88%). ESI-MS m/z calc. 392.4; found 393.1 (M+1)+ Retention time 3.17 minutes. 1H NMR (400 MHz, DMSO-d6) δ 11.80 (s, 1H), 8.64 (s, 1H), 7.83 (m, 1H), 7.33-7.26 (m, 2H), 7.07 (m, 1H), 7.02 (m, 1H), 6.96-6.89 (m, 2H), 6.02 (s, 2H), 4.33 (q, J=7.1 Hz, 2H), 1.42-1.39 (m, 2H), 1.33 (t, J=7.1 Hz, 3H), 1.06-1.03 (m, 2H).

Workup

  1. customThe excess thionyl chloride was removed under vacuum
  2. dissolutionthe resulting solid was dissolved in anhydrous dichloromethane (15 mL)
  3. stirringto stir for 1 hour
  4. washwashed three times with 50 mL of 1N HCl, saturated aqueous sodium bicarbonate, and saturated aqueous sodium chloride
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. customevaporated to dryness

Sources & evidence

ORD record
ord-c0eddd7e291b4071a12bd89afadf3589
Source dataset
uspto-grants-2015_02
Patent number
US08952050B2

Reaction notes

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