Tetrahydrofuran → HCID 86695076, compound

HRID 574349Notes

Reaction equation

HRID 574349 reaction equation
[C:1]1([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[N:30]=[C:10]3[N:11]=[C:12]([CH3:29])[C:13]([C:23](=[O:28])[C:24]([O:26][CH3:27])=[O:25])=[C:14]([N:15]4[CH2:20][CH2:19][C:18]([CH3:22])([CH3:21])[CH2:17][CH2:16]4)[N:9]3[N:8]=2)[CH:2]=1.CB1N2CCC[C@@H]2C(C2C=CC=CC=2)(C2C=CC=CC=2)O1.C1(C)C=CC=CC=1.C1COCC1>C1(C)C=CC=CC=1.CCOC(C)=O.C([O-])([O-])=O.[Na+].[Na+]>[C:1]1([C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[N:30]=[C:10]3[N:11]=[C:12]([CH3:29])[C:13]([C@H:23]([OH:28])[C:24]([O:26][CH3:27])=[O:25])=[C:14]([N:15]4[CH2:16][CH2:17][C:18]([CH3:22])([CH3:21])[CH2:19][CH2:20]4)[N:9]3[N:8]=2)[CH:2]=1

Participants

7

Reactant 3

HCID 8028TetrahydrofuranHCID 86670277(R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole tolueneHCID 86695074HCID 86695074, compound

Product 1

HCID 86695076HCID 86695076, compoundYield 92%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
-35 °C

Procedure

To a stirred yellow solution of methyl 2-(2-([1,1′-biphenyl]-3-yl)-7-(4,4-dimethylpiperidin-1-yl)-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetate (61 mg, 0.126 mmol) in anhydrous Toluene (6 mL) was added 1.1M (R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole/toluene (0.046 mL, 0.050 mmol). The mixture was cooled to −35° C. and a solution of 1M catechoborane/THF (0.177 mL, 0.177 mmol) was added over 10 min. After 30 min, the reaction mixture was slowly warmed to −15° C. and stirred for additional 2 h. and diluted with EtOAc (100 mL) and sat. Na2CO3 (50 mL). The mixture was stirred vigorously for 30 min, and the organic phase washed with sat Na2CO3 (2×50 mL), dried (Na2SO4), filtered, concentrated and the residue was purified by Biotage (5-70% EtOAc/hexane) to afford desired (S)-methyl 2-(2-([1,1′-biphenyl]-3-yl)-7-(4,4-dimethylpiperidin-1-yl)-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate (59 mg, 0.115 mmol, 92% yield).

Workup

  1. temperaturethe reaction mixture was slowly warmed to −15° C.
  2. stirringThe mixture was stirred vigorously for 30 min
  3. washthe organic phase washed
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customthe residue was purified by Biotage (5-70% EtOAc/hexane)

Sources & evidence

ORD record
ord-cbfeeb5665af404cbefa14b4c664186a
Source dataset
uspto-grants-2015_05
Patent number
US09034882B2

Reaction notes

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