Boc-D-phenylalanine → Methyl 5-[[5-bromo-4-(prop-2-ynyloxy)pyrimidin-2-yl]amino]-3-[[(2R)-2-[[(1,1-dimethylethoxy)carbonyl]amino]-1-oxo-3-phenylpropyl]amino]benzoate

HRID 1785316Notes

Reaction equation

HRID 1785316 reaction equation
[C:1]([NH:8][C@@H:9]([C:17]([OH:19])=O)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[NH2:43][C:44]1[CH:45]=[C:46]([CH:51]=[C:52]([NH:54][C:55]2[N:60]=[C:59]([O:61][CH2:62][C:63]#[CH:64])[C:58]([Br:65])=[CH:57][N:56]=2)[CH:53]=1)[C:47]([O:49][CH3:50])=[O:48]>CN(C=O)C.C(OCC)(=O)C>[Br:65][C:58]1[C:59]([O:61][CH2:62][C:63]#[CH:64])=[N:60][C:55]([NH:54][C:52]2[CH:53]=[C:44]([NH:43][C:17](=[O:19])[C@H:9]([NH:8][C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])[CH2:10][C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH:45]=[C:46]([CH:51]=2)[C:47]([O:49][CH3:50])=[O:48])=[N:56][CH:57]=1

Participants

7

Reactant 4

HCID 637610Boc-D-phenylalanineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 57593287Methyl 3-amino-5-[[5-bromo-4-(prop-2-ynyloxy)pyrimidin-2-yl]amino]benzoate

Product 1

HCID 86760835Methyl 5-[[5-bromo-4-(prop-2-ynyloxy)pyrimidin-2-yl]amino]-3-[[(2R)-2-[[(1,1-dimethylethoxy)carbonyl]amino]-1-oxo-3-phenylpropyl]amino]benzoateYield 83.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

N-BOC-D-phenylalanine (3.3 g), 1-hydroxy-1H-benzotriazole hydrate(1.9 g) and N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimid hydrochloride (2.37 g) were stirred in DMF (30 ml) for 30 minutes Then methyl 3-amino-5-[[5-bromo-4-(prop-2-ynyloxy)pyrimidin-2-yl]amino]benzoate (3.88 g) were added and the mixture stirred over night. Then ethyl acetate (500 ml) was added and the reaction mixture washed subsequently with hydrochloric acid (0.1 n), saturated NaHCO3-solution, water and brine. After drying (Na2SO4) the organic phase was evaporated and the residue subjected to column chromatography (ethyl acetate/dichloromethane) to yield 5.36 g of the title compound.

Workup

  1. washthe reaction mixture washed subsequently with hydrochloric acid (0.1 n), saturated NaHCO3-solution, water and brine
  2. dry with materialAfter drying (Na2SO4) the organic phase
  3. customwas evaporated

Sources & evidence

ORD record
ord-445f6cf854b840fb9be84fa43e1027e6
Source dataset
uspto-grants-2009_03
Patent number
US07504410B2

Reaction notes

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