Tetrahydrofuran → HCID 136009431, compound

HRID 1969667Notes

Reaction equation

HRID 1969667 reaction equation
[CH2:1]([C@H:3]1[C@@H:7]([C:8]2[N:12]3[C:13]4[CH:19]=[CH:18][NH:17][C:14]=4[N:15]=[CH:16][C:11]3=[N:10]N=2)[CH2:6][C@H:5]([CH2:20]C(OCC)=O)[CH2:4]1)[CH3:2].[Cl-].[Li+].[CH3:28][Mg]Br.[NH4+:31].[Cl-].[CH2:33]1[CH2:37][O:36]CC1>CCOCC.CCOC(C)=O>[CH2:1]([C@H:3]1[C@@H:7]([C:8]2[N:12]3[C:13]4[CH:19]=[CH:18][NH:17][C:14]=4[N:15]=[CH:16][C:11]3=[N:10][N:31]=2)[CH2:6][C@H:5]([CH2:20][C:37]([CH3:33])([OH:36])[CH3:28])[CH2:4]1)[CH3:2]

Participants

8

Reactant 5

HCID 8028Tetrahydrofuran2×HCID 25517Ammonium ChlorideHCID 433294Lithium ChlorideHCID 136009214HCID 136009214, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 136009431HCID 136009431, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of ethyl 2-((1R,3R,4S)-3-ethyl-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)acetate (0.166 g, 0.486 mmol, Example #38, Step H) in THF (4 mL) at about 0° C. was added lithium chloride in THF (0.5 M, 3.9 mL) followed by methylmagnesium bromide in Et2O (3.0 M, 0.65 mL). After about 20 min the reaction mixture was allowed to warm to rt. After about 4 h the reaction mixture was cooled to about −78° C. and saturated aqueous NH4Cl (about 5 mL) was added. After about 5 min the reaction mixture was allowed to warm to rt and EtOAc (about 10 mL) was added. The layers were separated and the organic solution was dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The crude material was purified by silica gel chromatography eluting with EtOAc/MeOH to provide 1-((1R,3R,4S)-3-ethyl-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)-2-methylpropan-2-ol (0.118 g, 74%) as a foam: LC/MS (Table 1, Method a) Rt=1.64 min; MS m/z 328 (M+H)+.

Workup

  1. temperatureAfter about 4 h the reaction mixture was cooled to about −78° C.
  2. waitAfter about 5 min the reaction mixture was allowed
  3. temperatureto warm to rt
  4. customThe layers were separated
  5. dry with materialthe organic solution was dried over anhydrous MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was purified by silica gel chromatography
  9. washeluting with EtOAc/MeOH

Sources & evidence

ORD record
ord-7c58b6b4f5a94adcb5d05aef95cee238
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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