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 2233471Notes

Reaction equation

HRID 2233471 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-312a92da22a648588d0b3e4297555940
Source dataset
uspto-grants-2010_05
Patent number
US07709493B2

Reaction notes

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