Potassium Phosphate, Tribasic → HCID 69508751, compound

HRID 1354055Notes

Reaction equation

HRID 1354055 reaction equation
[CH2:1]([O:3][C:4](=[O:37])[CH2:5][C@@H:6]([NH:21][C:22]1[C:27](Br)=[CH:26][N:25]=[C:24]([N:29]([CH:31]2[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]2)[CH3:30])[N:23]=1)[C:7]1[CH:12]=[CH:11][C:10]([O:13][Si](C(C)(C)C)(C)C)=[CH:9][CH:8]=1)[CH3:2].[F:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=1B(O)O.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([O:3][C:4](=[O:37])[CH2:5][C@@H:6]([NH:21][C:22]1[C:27]([C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=2[F:38])=[CH:26][N:25]=[C:24]([N:29]([CH:31]2[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36]2)[CH3:30])[N:23]=1)[C:7]1[CH:8]=[CH:9][C:10]([OH:13])=[CH:11][CH:12]=1)[CH3:2]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27343542-Fluorophenylboronic acidHCID 69508896HCID 69508896, compound

Product 1

HCID 69508751HCID 69508751, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A suspension of (R)-3-(5-bromo-2-(N-cyclohexyl-N-methylamino)pyrimidin-4-ylamino)-3-(4-(tert-butyldimethylsiloxy)phenyl)propanoic acid ethyl ester (1.0 eq), 2-fluorophenylboronic acid (3.0 eq), K3PO4 (3.0 eq) and Pd(PPh3)4 (0.03 eq) in DMF under nitrogen was stirred at 90° C. for 5 h. The DMF was evaporated, the residue was dissolved in EtOAc, and the resulting solution was washed successively with 0.5 M citric acid, sat. NaHCO3 and sat. NaCl. The EtOAc extracts were treated with MgSO4, filtered, and evaporated. The residue was purified by flash chromatography on silica gel using 6:4 hexanes/EtOAc to give (R)-3-(5-(2-fluorophenyl)-2-(N-cyclohexyl-N-methylamino)pyrimidin-4-ylamino)-3-(4-hydroxyphenyl)propanoic acid ethyl ester.

Workup

  1. customThe DMF was evaporated
  2. dissolutionthe residue was dissolved in EtOAc
  3. washthe resulting solution was washed successively with 0.5 M citric acid, sat. NaHCO3 and sat. NaCl
  4. additionThe EtOAc extracts were treated with MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by flash chromatography on silica gel using 6:4 hexanes/EtOAc

Sources & evidence

ORD record
ord-530e0f99e4584bac98622595ca1212cf
Source dataset
uspto-grants-2007_05
Patent number
US07223762B2

Reaction notes

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