Hexane → tert-Butyl {[(E)-2-((1S,2S,4R)-2-{[tert-butyl(dimethyl)silyl]oxy}-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}cyclopentyl)vinyl]sulfonyl}carbamate

HRID 222206Notes

Reaction equation

HRID 222206 reaction equation
[C:1]([O:5][C:6](=[O:26])[NH:7][S:8]([CH2:11]P(C1C=CC=CC=1)(C1C=CC=CC=1)=O)(=[O:10])=[O:9])([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.CCCCCC.[Si:38]([O:45][C@H:46]1[CH2:50][C@H:49]([N:51]2[C:55]3[N:56]=[CH:57][N:58]=[C:59]([NH:60][C@@H:61]4[C:69]5[C:64](=[CH:65][CH:66]=[CH:67][CH:68]=5)[CH2:63][CH2:62]4)[C:54]=3[CH:53]=[CH:52]2)[CH2:48][C@H:47]1[CH:70]=O)([C:41]([CH3:44])([CH3:43])[CH3:42])([CH3:40])[CH3:39]>C1COCC1>[C:1]([O:5][C:6](=[O:26])[NH:7][S:8](/[CH:11]=[CH:70]/[C@@H:47]1[CH2:48][C@@H:49]([N:51]2[C:55]3[N:56]=[CH:57][N:58]=[C:59]([NH:60][C@@H:61]4[C:69]5[C:64](=[CH:65][CH:66]=[CH:67][CH:68]=5)[CH2:63][CH2:62]4)[C:54]=3[CH:53]=[CH:52]2)[CH2:50][C@@H:46]1[O:45][Si:38]([C:41]([CH3:43])([CH3:44])[CH3:42])([CH3:39])[CH3:40])(=[O:10])=[O:9])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 8058HexaneHCID 11395320tert-Butyl ((diphenylphosphoryl)methyl)sulfonylcarbamateHCID 58944601(1R,2S,4R)-2-[tert-butyl(dimethyl)silyl]oxy-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}cyclopentanecarbaldehydeHCID 178418339Butyllithium

Product 1

HCID 68057837tert-Butyl {[(E)-2-((1S,2S,4R)-2-{[tert-butyl(dimethyl)silyl]oxy}-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}cyclopentyl)vinyl]sulfonyl}carbamateYield 21.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

tert-Butyl{[(diphenylphosphoryl)methyl]sulfonyl}carbamate (602 mg, 1.45 mmol) was dissolved in THF (50.0 mL) under an atmosphere of argon, a 1.60 M solution of n-butyllithium in hexane (1.81 mL, 2.89 mmol) was added at −50° C., and the resultant mixture was stirred for 1 h. A solution of (1R,2S,4R)-2-{[tert-butyl(dimethyl)silyl]oxy}-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}cyclopentanecarbaldehyde (300 mg, 0.60 mmol) in THF (8.0 mL) was added to the mixture, and the resulting mixture was stirred for 30 min at room temperature. After quenching by addition of water (200 mL), the mixture was extracted with EtOAc (100 mL×3). The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified via silica gel chromatography eluting with a gradient of 10 to 60% EtOAc in hexane to afford the title compound (84.0 mg, 21%). LC/MS: Rt=1.90 min, ES+ 654 (FA standard).

Workup

  1. customAfter quenching by addition of water (200 mL)
  2. extractionthe mixture was extracted with EtOAc (100 mL×3)
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified via silica gel chromatography
  7. washeluting with a gradient of 10 to 60% EtOAc in hexane

Sources & evidence

ORD record
ord-53067b79fb174fd2a7d592997e3c57c4
Source dataset
uspto-grants-2012_06
Patent number
US08207177B2

Reaction notes

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