Potassium Carbonate → HCID 67436440, compound

HRID 1968888Notes

Reaction equation

HRID 1968888 reaction equation
[C:1]([O:5][C:6](=[O:34])[NH:7][C@H:8]([CH2:13][N:14]([C:22]([C@@H:24]1[CH2:26][C@H:25]1[C:27]1[CH:32]=[CH:31][C:30]([F:33])=[CH:29][N:28]=1)=[O:23])[C:15]1[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=1)[C@@H:9]([CH3:12])[CH2:10][CH3:11])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].[CH:41]1([CH2:45]Br)[CH2:44][CH2:43][CH2:42]1>CN(C=O)C>[C:1]([O:5][C:6](=[O:34])[NH:7][C@H:8]([CH2:13][N:14]([C:15]1[CH:16]=[CH:17][C:18]([O:21][CH2:45][CH:41]2[CH2:44][CH2:43][CH2:42]2)=[CH:19][CH:20]=1)[C:22]([C@@H:24]1[CH2:26][C@H:25]1[C:27]1[CH:32]=[CH:31][C:30]([F:33])=[CH:29][N:28]=1)=[O:23])[C@@H:9]([CH3:12])[CH2:10][CH3:11])([CH3:3])([CH3:4])[CH3:2]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 2734658(Bromomethyl)cyclobutaneHCID 67436478HCID 67436478, compound

Product 1

HCID 67436440HCID 67436440, compoundYield 89.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

A mixture of ((1S,2S)-1-{[[(1R,2R)-2-(5-fluoro-pyridin-2-yl)-cyclopropanecarbonyl]-(4-hydroxy-phenyl)-amino]-methyl}-2-methyl-butyl)-carbamic acid tert-butyl ester (51 mg, 0.11 mmol), K2CO3 (69 mg, 0.5 mmol) and cyclobutylmethyl bromide (22 mg, 0.15 mmol) in DMF was stirred at 55° C. for over night. After cool to rt, the mixture was filtered through a silica pad (EtOAc). The filtrate was concentrated and the residue was subjected to ISCO (12 g column, 0-40% EtOAc in hexane over 25 min) to give the titled compound (53 mg). MS (MH+ 540).

Workup

  1. temperatureAfter cool to rt
  2. filtrationthe mixture was filtered through a silica pad (EtOAc)
  3. concentrationThe filtrate was concentrated
  4. customwas subjected to ISCO (12 g column, 0-40% EtOAc in hexane over 25 min)

Sources & evidence

ORD record
ord-dbd66b32acbc448ab9263ac65c6c59dd
Source dataset
uspto-grants-2013_04
Patent number
US08426414B2

Reaction notes

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