Tetrabutylammonium Fluoride → 7-[1-[(Tert-butoxycarbonylamino)methyl]-2-methyl-propyl]-2-chloro-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid

HRID 70768Notes

Reaction equation

HRID 70768 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH2:10][NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[C:5]([C:19]#[C:20][CH:21]([O:25]CC)[O:22]CC)=[CH:4][N:3]=1.[CH3:28][CH2:29][CH2:30]C[N+](CCCC)(CCCC)CCCC.[F-].OOS([O-])=O.[K+]>C1COCC1.CN(C=O)C.C(OCC)(=O)C.C(O)(=O)C.O.O>[C:14]([O:13][C:12]([NH:11][CH2:10][CH:9]([N:8]1[C:6]2[N:7]=[C:2]([Cl:1])[N:3]=[CH:4][C:5]=2[CH:19]=[C:20]1[C:21]([OH:22])=[O:25])[CH:29]([CH3:30])[CH3:28])=[O:18])([CH3:15])([CH3:16])[CH3:17]

Participants

9

Reactant 3

HCID 2724141Tetrabutylammonium FluorideHCID 23707502Potassium hydroxy sulfiteHCID 86695595tert-butyl N-[2-[[2-chloro-5-(3,3-diethoxyprop-1-ynyl)pyrimidin-4-yl]amino]ethyl]carbamate

Product 1

HCID 866955947-[1-[(Tert-butoxycarbonylamino)methyl]-2-methyl-propyl]-2-chloro-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×HCID 21899381Acetic acid--water (1/1)Solvent

Procedure

To a solution tert-butyl N-[2-[[2-chloro-5-(3,3-diethoxyprop-1-ynyl)pyrimidin-4-yl]amino]ethyl]carbamate in THF was added TBAF and the contents refluxed for 3 hrs. Ethyl acetate and water was then added and the organic layer separated, dried with magnesium sulfate and then concentrated under vacuum. To this crude reaction was added acetic acid/water (9:1) and then contents stirred for 12 hrs at room temperature. After concentration under vacuum, sat NaHCO3 and ethyl acetate was then added. The organic layer was separated, dried and then concentrated under vacuum. The crude reaction product thus obtained was dissolved in DMF, oxone was then added and the contents stirred for 3 hrs. After addition of ethyl acetate, the reaction mixture was filtered through CELITE™ and concentrated under vacuum. Column chromatography of the crude product over silica gel using hexane/ethyl acetate (0-100%) afforded 7-[1-[(tert-butoxycarbonylamino)methyl]-2-methyl-propyl]-2-chloro-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid. 1H NMR (600 MHz, DMSO-d6) δ ppm 0.85 (d, J=7.03 Hz, 3H) 0.97 (d, J=6.73 Hz, 3H) 1.52 (s, 9H) 1.99-2.23 (m, 1H) 3.98 (dd, J=14.05, 3.51 Hz, 1H) 4.47-4.71 (m, 2H) 7.47 (s, 1H) 9.17 (s, 1H). LCMS (ESI) 383 (M+H).

Workup

  1. temperaturethe contents refluxed for 3 hrs
  2. customthe organic layer separated
  3. dry with materialdried with magnesium sulfate
  4. concentrationconcentrated under vacuum
  5. customTo this crude reaction
  6. concentrationAfter concentration under vacuum
  7. additionwas then added
  8. customThe organic layer was separated
  9. customdried
  10. concentrationconcentrated under vacuum
  11. customThe crude reaction product
  12. customthus obtained
  13. stirringthe contents stirred for 3 hrs
  14. filtrationthe reaction mixture was filtered through CELITE™
  15. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-cb4f5373e31a42d09a4d2f254201c193
Source dataset
uspto-grants-2014_09
Patent number
US08822683B2

Reaction notes

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