Dicyclohexylcarbodiimide → tert-butyl-N-[1-[[5-bromo-6-(2-phenylethynyl)pyridin-2-yl]amino]-1-oxo-propan-2-yl]-N-methylcarbamate

HRID 535387

Reaction equation

HRID 535387 reaction equation
[CH3:1][N:2]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH:3]([CH3:7])[C:4]([OH:6])=O.C1(N=C=NC2CCCCC2)CCCCC1.[Br:30][C:31]1[CH:32]=[CH:33][C:34]([NH2:45])=[N:35][C:36]=1[C:37]#[C:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1>C(Cl)Cl>[C:11]([O:10][C:8](=[O:9])[N:2]([CH:3]([CH3:7])[C:4]([NH:45][C:34]1[CH:33]=[CH:32][C:31]([Br:30])=[C:36]([C:37]#[C:38][C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=2)[N:35]=1)=[O:6])[CH3:1])([CH3:14])([CH3:13])[CH3:12]

Participants

5

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 44368572-(((Tert-butoxy)carbonyl)(methyl)amino)propanoic acidHCID 86694367HCID 86694367, compound

Product 1

HCID 86694372tert-butyl-N-[1-[[5-bromo-6-(2-phenylethynyl)pyridin-2-yl]amino]-1-oxo-propan-2-yl]-N-methylcarbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A mixture of 2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]propanoic acid (36 g, 177 mmol) and N,N′-dicyclohexylcarbodiimide (22.5 g, 109 mmol) in DCM (150 ml) is stirred with ice bath cooling for 30 minutes. A solution of 5-bromo-6-(2-phenylethynyl)pyridin-2-amine B2a (20 g, 73.2 mmol) in DCM (100 ml) is added. After stirring for 7 days at RT the reaction mixture is diluted with DCM and extracted with water. The combined organic layers are dried over MgSO4 and concentrated in vacuo. The product is purified by NP chromatography. Yield: 25 g (74%). HPLC-MS: M+H=458/460; tR=2.33 min (*Method—1).

Workup

  1. temperaturecooling for 30 minutes
  2. stirringAfter stirring for 7 days at RT the reaction mixture
  3. extractionextracted with water
  4. dry with materialThe combined organic layers are dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe product is purified by NP chromatography

Sources & evidence

ORD record
ord-d0dda53cdc214083ae398d2e611f12cf
Source dataset
uspto-grants-2014_10
Patent number
US08859541B2

Linked notes

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