Acetate → Methyl 6-{1-hydroxy-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethyl}pyridine-3-carboxylate

HRID 1040192Notes

Reaction equation

HRID 1040192 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]([C:11]2[S:12][C:13]([C:16]3[CH:21]=[C:20]([NH:22][C:23]4C=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[CH:25][N:24]=4)[CH:19]=[C:18]([CH3:33])[CH:17]=3)=[CH:14][N:15]=2)([OH:10])[CH3:9])=[N:6][CH:7]=1.[C:34]([O-:37])(=O)C.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([N:69](CC)CC)C.CN([CH:77]=[O:78])C>[NH4+].[Cl-].[Pd].CO>[OH:10][C:8]([C:5]1[N:6]=[CH:7][C:2]([C:34]([O:78][CH3:77])=[O:37])=[CH:3][CH:4]=1)([C:11]1[S:12][C:13]([C:16]2[CH:21]=[C:20]([NH:22][C:23]3[N:69]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[CH:25][N:24]=3)[CH:19]=[C:18]([CH3:33])[CH:17]=2)=[CH:14][N:15]=1)[CH3:9]

Participants

9

Reactant 5

HCID 175AcetateHCID 6228DimethylformamideHCID 8471TriethylamineHCID 812191,3-Bis(diphenylphosphino)propaneHCID 674303841-(5-Bromopyridin-2-yl)-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyridin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethanol

Product 1

HCID 67430861Methyl 6-{1-hydroxy-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethyl}pyridine-3-carboxylateYield 82%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
70 °C

Procedure

The product of Step 1 (500 mg, 0.932 mmol), palladium (TT) acetate (20.93 mg, 0.093 mmol), and 1,3-bis(diphenylphosphino)propane (38.4 mg, 0.093 mmol) were combined in a 5 ml microwave vial, sealed, and taken up in DMF (4 ml)/MeOH (2.000 ml). CO was bubbled through the reaction mixture for 5 min. Triethylamine (0.260 ml, 1.864 mmol) was added, a CO balloon was attached, and the reaction was stirred at 70° C. for 2 days. The reaction was diluted with aqueous saturated NH4Cl and extracted with EtOAc (2×). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated. Chromatography on silica gel (Biotage 100 g SNAP, 0-50% EtOAc/hexanes) provided methyl 6-{1-hydroxy-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethyl}pyridine-3-carboxylate (392 mg, 0.760 mmol, 82% yield) as a pale yellow foam. MS ESI: [M+H]+ m/z 516.1.

Workup

  1. customsealed
  2. customCO was bubbled through the reaction mixture for 5 min
  3. extractionextracted with EtOAc (2×)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-f76b9f6c66124e53abefca08303f0527
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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