1,2-Dichloroethane → (4-bromo-1H-indol-2-yl)(pyrrolidin-1-yl)methanone

HRID 661838Notes

Reaction equation

HRID 661838 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([C:11]([OH:13])=O)[NH:6]2.[NH:14]1[CH2:18][CH2:17][CH2:16][CH2:15]1.C1C=NC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.C(Cl)CCl>C(#N)C.CCOC(C)=O>[Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([C:11]([N:14]1[CH2:18][CH2:17][CH2:16][CH2:15]1)=[O:13])[NH:6]2

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 40426044-bromo-1H-indole-2-carboxylic acid

Product 1

HCID 59375103(4-bromo-1H-indol-2-yl)(pyrrolidin-1-yl)methanoneYield 67.2%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4-bromo-1H-indole-2-carboxylic acid (250 mg, 1.04 mmol), pyrrolidine (0.129 mL, 1.56 mmol), and HOAT (213 mg, 1.56 mmol) in acetonitrile (5 mL) was treated with DIEA (0.364 mL, 2.08 mmol) and EDC (399 mg, 2.08 mmol) and the mixture was stirred at rt. After 18.25 h, the mixture was diluted with EtOAc, filtered to remove some tan solid, and washed sequentially with 1 M hydrochloric acid and NaHCO3 (aq), and dried and concentrated to provide (4-bromo-1H-indol-2-yl)(pyrrolidin-1-yl)methanone as a tan solid (205 mg, 67%). 1H NMR (400 MHz, DMSO-d6) δ 11.96 (s, 1H) 7.46 (d, J=7.9 Hz, 1H) 7.27 (d, J=7.5 Hz, 1H) 7.06-7.17 (m, 1H) 6.82 (s, 1H) 3.85 (t, J=6.8 Hz, 2H) 3.55 (t, J=6.8 Hz, 2H) 1.93-2.04 (m, 2H) 1.81-1.92 (m, 2H). Mass spectrum m/z 293, 295 (M+H)+.

Workup

  1. filtrationfiltered
  2. customto remove some tan solid
  3. washwashed sequentially with 1 M hydrochloric acid and NaHCO3 (aq)
  4. customdried
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-2856a29f29544000a1c8084fe7722a23
Source dataset
uspto-grants-2011_12
Patent number
US08084620B2

Reaction notes

Loading…