Cesium carbonate → (S)-2-Amino-3-[4-(2-amino-6-{2,2,2-trifluoro-1-[5-methoxy-2-(4-methyl-pyrazol-1-yl)-phenyl]-ethoxy}-pyrimidin-4-yl)-phenyl]-propionic acid

HRID 1988039Notes

Reaction equation

HRID 1988039 reaction equation
[F:1][C:2]([F:20])([F:19])[CH:3]([C:5]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[CH:7][C:6]=1[N:13]1[CH:17]=[C:16]([CH3:18])[CH:15]=[N:14]1)[OH:4].[NH2:21][C:22]1[N:27]=[C:26]([C:28]2[CH:33]=[CH:32][C:31]([CH2:34][C@H:35]([NH:39]C(OC(C)(C)C)=O)[C:36]([OH:38])=[O:37])=[CH:30][CH:29]=2)[CH:25]=[C:24](Cl)[N:23]=1.O1CCOCC1.C([O-])([O-])=O.[Cs+].[Cs+]>C(O)(C(F)(F)F)=O.C(Cl)Cl>[NH2:39][C@@H:35]([CH2:34][C:31]1[CH:32]=[CH:33][C:28]([C:26]2[CH:25]=[C:24]([O:4][CH:3]([C:5]3[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[CH:7][C:6]=3[N:13]3[CH:17]=[C:16]([CH3:18])[CH:15]=[N:14]3)[C:2]([F:19])([F:1])[F:20])[N:23]=[C:22]([NH2:21])[N:27]=2)=[CH:29][CH:30]=1)[C:36]([OH:38])=[O:37]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 251913394-(2-Amino-6-chloropyrimidin-4-yl)-N-(tert-butoxycarbonyl)-L-phenylalanineHCID 667434242,2,2-Trifluoro-1-[5-methoxy-2-(4-methyl-pyrazol-1-yl)-phenyl]-ethanol

Product 1

HCID 25025103(S)-2-Amino-3-[4-(2-amino-6-{2,2,2-trifluoro-1-[5-methoxy-2-(4-methyl-pyrazol-1-yl)-phenyl]-ethoxy}-pyrimidin-4-yl)-phenyl]-propionic acid

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
180 °C

Procedure

2,2,2-Trifluoro-1-[5-methoxy-2-(4-methyl-pyrazol-1-yl)-phenyl]-ethanol (0.090 g, 0.31 mmol), (S)-3-[4-(2-amino-6-chloro-pyrimidine-4-yl)-phenyl]-2-tert-butoxycarbonylamino-propionic acid (0.122 g, 0.31 mmol), 1,4-dioxane (2 ml), Cs2CO3 (0.503 g, 1.55 mmol) were combined in a microwave vial and heated to 180° C. for 45 min. The mixture was filtered and concentrated. To the residue, 5% methanol in DCM (50 ml) was added. The mixture was filtered. The filtrate was concentrated to give crude product which was taken in 20% TFA in DCM (30 ml) and stirred for 30 minutes at room temperature. LCMS indicated the completion of the reaction with desired product. The reaction mixture was concentrated to give crude product, which was dissolved in MeOH and H2O (1:1), and purified by preparative HPLC using MeOH/H2O/TFA as solvent system to give (S)-2-amino-3-[4-(2-amino-6-{2,2,2-trifluoro-1-[5-methoxy-2-(4-methyl-pyrazol-1-yl)-phenyl]-ethoxy]-pyrimidin-4-yl)-phenyl]-propionic acid.

Workup

  1. filtrationThe mixture was filtered
  2. concentrationconcentrated
  3. additionTo the residue, 5% methanol in DCM (50 ml) was added
  4. filtrationThe mixture was filtered
  5. concentrationThe filtrate was concentrated
  6. customto give crude product which

Sources & evidence

ORD record
ord-597dfff56d4946aa9ba10dadaac2711a
Source dataset
uspto-grants-2009_06
Patent number
US07553840B2

Reaction notes

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