1,3-Dibromopropane → HCID 59224762, compound

HRID 2078728Notes

Reaction equation

HRID 2078728 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([OH:17])[CH:15]=2)[CH:10]=[C:9]1[C:18]1[C:19]2[S:32][C:31]([C:33]3[CH:38]=[CH:37][CH:36]=[C:35]([O:39][CH3:40])[CH:34]=3)=[CH:30][C:20]=2[N:21]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[N:22]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].[Br:47][CH2:48][CH2:49][CH2:50]Br>>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:17][CH2:50][CH2:49][CH2:48][Br:47])[CH:15]=2)[CH:10]=[C:9]1[C:18]1[C:19]2[S:32][C:31]([C:33]3[CH:38]=[CH:37][CH:36]=[C:35]([O:39][CH3:40])[CH:34]=3)=[CH:30][C:20]=2[N:21]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[N:22]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

4

Reactant 3

HCID 80011,3-DibromopropaneHCID 10796Cesium carbonateHCID 136016244HCID 136016244, compound2×

Product 1

HCID 59224762HCID 59224762, compoundYield 76%

Conditions

Temperature
75 °C

Procedure

A mixture of 2-[1-tert-butoxycarbonyl-5-(3-methoxy-phenyl)-1H-thieno[3,2-c]pyrazol-3-yl]-6-hydroxy-indole-1-carboxylic acid tert-butyl ester [1.19 g, 2.12 mmol, Intermediate (57)], cesium carbonate (2.07 g, 6.35 mmol), and 1,3-dibromopropane (8.0 mL) was heated at 75° C. under nitrogen. After 6 hours, the mixture was cooled to ambient temperature and let stand overnight. The mixture was filtered, and the insolubles washed twice with dichloromethane (10 mL). The filtrate was concentrated in vacuo to yield a golden oil. The crude product was chromatographed on silica, eluting with a gradient of 30% ethyl acetate/heptane to 50% ethyl acetate/heptane to give 6-(3-bromo-propoxy)-2-[1-tert-butoxycarbonyl-5-(3-methoxy-phenyl)-1H-thieno[3,2-c]pyrazol-3-yl]-indole-1-carboxylic acid tert-butyl ester [1.11 g, 76%, Intermediate (58)] as a white foam. TLC Rf 0.46 (silica, 40% ethyl acetate/heptane); LC/MS: 682.2 (M+H), RT=3.23 minutes.

Workup

  1. temperaturethe mixture was cooled to ambient temperature
  2. waitlet stand overnight
  3. filtrationThe mixture was filtered
  4. washthe insolubles washed twice with dichloromethane (10 mL)
  5. concentrationThe filtrate was concentrated in vacuo
  6. customto yield a golden oil
  7. customThe crude product was chromatographed on silica
  8. washeluting with a gradient of 30% ethyl acetate/heptane to 50% ethyl acetate/heptane

Sources & evidence

ORD record
ord-8d7b506a52ab4d69b1a8eea9a42982a1
Source dataset
uspto-grants-2011_04
Patent number
US07928231B2

Reaction notes

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