Water → (S)-3-[4-(2-Amino-6-{2,2,2-trifluoro-1-[4-(6-methoxy-pyridin-2-yl)-phenyl]-ethoxy}-pyrimidin-4-yl)-phenyl]-2-tert-butoxycarbonylamino-propionic acid

HRID 1988046Notes

Reaction equation

HRID 1988046 reaction equation
C([O-])([O-])=O.[Cs+].[Cs+].[CH3:7][O:8][C:9]1[N:14]=[C:13]([C:15]2[CH:20]=[CH:19][C:18]([CH:21]([OH:26])[C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=2)[CH:12]=[CH:11][CH:10]=1.[NH2:27][C:28]1[N:33]=[C:32]([C:34]2[CH:39]=[CH:38][C:37]([CH2:40][C@H:41]([NH:45][C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[C:42]([OH:44])=[O:43])=[CH:36][CH:35]=2)[CH:31]=[C:30](Cl)[N:29]=1.O>O1CCOCC1.C(OCC)(=O)C>[NH2:27][C:28]1[N:33]=[C:32]([C:34]2[CH:39]=[CH:38][C:37]([CH2:40][C@H:41]([NH:45][C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[C:42]([OH:44])=[O:43])=[CH:36][CH:35]=2)[CH:31]=[C:30]([O:26][CH:21]([C:18]2[CH:19]=[CH:20][C:15]([C:13]3[CH:12]=[CH:11][CH:10]=[C:9]([O:8][CH3:7])[N:14]=3)=[CH:16][CH:17]=2)[C:22]([F:23])([F:24])[F:25])[N:29]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 251913394-(2-Amino-6-chloropyrimidin-4-yl)-N-(tert-butoxycarbonyl)-L-phenylalanineHCID 667436631-[4-(6-Methoxy-pyridine-2-yl)-phenyl]-2,2,2-trifluoro-ethanol

Product 1

HCID 66743335(S)-3-[4-(2-Amino-6-{2,2,2-trifluoro-1-[4-(6-methoxy-pyridin-2-yl)-phenyl]-ethoxy}-pyrimidin-4-yl)-phenyl]-2-tert-butoxycarbonylamino-propionic acidYield 88%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

Cs2CO3 (375 mg, 1 mmol) was added to a solution of 1-[4-(6-methoxy-pyridine-2-yl)-phenyl]-2,2,2-trifluoro-ethanol (67 mg, 0.2 mmol) in 10 ml of anhydrous 1,4-dioxane. The mixture was stirred for 5 min, then was added (S)-3-[4-(2-amino-6-chloro-pyrimidin-4-yl)-phenyl]-2-tert-butoxycarbonylamino-propionic acid (78 mg, 0.2 mmol), and the mixture was heated at 110° C. overnight. After cooling, 5 ml water was added and ethyl acetate (20 ml) was used to extract the product. The organic layer was dried over sodium sulfate. The solvent was removed by rotovap to give 112 mg (S)-3-[4-(2-Amino-6-{2,2,2-trifluoro-1-[4-(6-methoxy-pyridin-2-yl)-phenyl]-ethoxy}-pyrimidin-4-yl)-phenyl]-2-tert-butoxycarbonylamino-propionic acid (yield: 88%).

Workup

  1. temperatureAfter cooling
  2. extractionto extract the product
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. customThe solvent was removed by rotovap

Sources & evidence

ORD record
ord-eca4aab96b2f4849a253a967543acde1
Source dataset
uspto-grants-2009_06
Patent number
US07553840B2

Reaction notes

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