1,3-Dibromopropane → HCID 57637347, compound

HRID 2078720Notes

Reaction equation

HRID 2078720 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]=[CH:35][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:45][CH2:46][CH2:47][CH2:48]Br>>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:17][CH2:48][CH2:47][CH2:46][Br:45])[CH:15]=2)[CH:10]=[C:9]1[C:18]1[C:19]2[S:32][C:31]([C:33]3[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=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 136016222HCID 136016222, compound2×

Product 1

HCID 57637347HCID 57637347, compoundYield 65%

Conditions

Temperature
90 °C

Procedure

A mixture of 2-(1-tert-butoxycarbonyl-5-phenyl-1H-thieno[3,2-c]pyrazol-3-yl)-6-hydroxy-indole-1-carboxylic acid tert-butyl ester [950 mg, 1.79 mmol, Intermediate (49)], cesium carbonate (1.75 g, 5.37 mmol), and 1,3-dibromopropane (6.0 mL) was heated at 90° C. under nitrogen. After 1.5 hours, the mixture was cooled to ambient temperature, filtered, and the insolubles washed twice with dichloromethane (10 mL). The filtrate was concentrated in vacuo to yield a cloudy oil. The crude product was chromatographed on silica, eluting first with 80% dichloromethane/heptane and then 100% dichloromethane to give 6-(3-bromo-propoxy)-2-(1-tert-butoxycarbonyl-5-phenyl-1H-thieno[3,2-c]pyrazol-3-yl)-indole-1-carboxylic acid tert-butyl ester [760 mg, 65%, intermediate 50] as a white foam. TLC Rf 0.37 (silica, dichloromethane); LC/MS: 674 (M+Na), RT=2.60 minutes.

Workup

  1. temperaturethe mixture was cooled to ambient temperature
  2. filtrationfiltered
  3. washthe insolubles washed twice with dichloromethane (10 mL)
  4. concentrationThe filtrate was concentrated in vacuo
  5. customto yield a cloudy oil
  6. customThe crude product was chromatographed on silica
  7. washeluting first with 80% dichloromethane/heptane

Sources & evidence

ORD record
ord-2abe00629894402ea4874deb16069617
Source dataset
uspto-grants-2011_04
Patent number
US07928231B2

Reaction notes

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