Dimethylformamide → HCID 22638736, compound

HRID 2416245Notes

Reaction equation

HRID 2416245 reaction equation
C(Cl)(=O)C(Cl)=O.CN(C=O)C.[OH:12][CH2:13][CH2:14][CH:15]1[CH2:17][CH:16]1[C:18]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([C:27]#[N:28])[CH:25]=2)[N:20]([S:29]([C:32]2[CH:37]=[CH:36][C:35]([CH3:38])=[CH:34][CH:33]=2)(=[O:31])=[O:30])[CH:19]=1.C(N(CC)CC)C>C(Cl)Cl>[O:12]=[CH:13][CH2:14][CH:15]1[CH2:17][CH:16]1[C:18]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([C:27]#[N:28])[CH:25]=2)[N:20]([S:29]([C:32]2[CH:37]=[CH:36][C:35]([CH3:38])=[CH:34][CH:33]=2)(=[O:31])=[O:30])[CH:19]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 22638724HCID 22638724, compound

Product 1

HCID 22638736HCID 22638736, compoundYield 67.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

Oxalyl chloride (0.5 ml of 2.0 M solution in methylene chloride, 1.0 mmol) was diluted with dry methylene chloride (5.0 ml) and cooled to −78° C. under a nitrogen atmosphere. DMF (0.08 ml, 1.12 mmol) was added via a micro syringe and the solution was stirred at −78° C. for 10 min. A solution of 3-[2-(2-hydroxy-ethyl)cyclopropyl]-1-(toluene-4sulfonyl)-1H-indole-5-carbonitrile (250 mg, 0.657 mmol) in dry methylene chloride (5 ml) was added drop wise, and the solution was stirred at −78° C. for 1 hr, and then triethylamine (1.0 ml) was added. The solution was concentrated in vacuo, and the residue was dissolved in ethyl acetate (10 ml). The ethyl acetate solution was extracted with HCl (5 ml of 1 N solution), and with brine (5 ml). The ethyl acetate solution was dried over sodium sulfate and concentrated in vacuo. The residue was chromatographed on silica gel using methylene chloride as the eluent to give 3-[2-(2-oxo-ethyl)-cyclopropyl]-1-(toluene-4-sulfonyl)-1H-indole-5-carbonitrile (167 mg, 67%). 1H NMR (500 MHz, CDCl3): δ 9.87 (s, 1H), 8.03 (d,1H), 7.96 (s, 1H), 7.74 (d, 2H), 7.56 (d, 1H), 7.35 (s, 1H), 7.25 (d, 2H), 2.59 (m, 2H), 2.36 (s, 3H), 1.67 (m, 1H), 1.30 (m, 1H), 1.30 (m, 1H), 1.02 (m, 1H), 0.89 (m, 1H). MS m/e 379.16 (MH+).

Workup

  1. stirringthe solution was stirred at −78° C. for 1 hr
  2. concentrationThe solution was concentrated in vacuo
  3. dissolutionthe residue was dissolved in ethyl acetate (10 ml)
  4. extractionThe ethyl acetate solution was extracted with HCl (5 ml of 1 N solution)
  5. dry with materialThe ethyl acetate solution was dried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-99997f1cc1064c048831d5a68f695aea
Source dataset
uspto-grants-2004_11
Patent number
US06822100B2

Reaction notes

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