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

HRID 2362282노트

반응식

HRID 2362282 반응식
[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]

참가 물질

9

반응물 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

생성물 1

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

시약·촉매·용매 5

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매2회HCID 21899381Acetic acid--water (1/1)용매

실험 절차

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, 3 H) 0.97 (d, J=6.73 Hz, 3 H) 1.52 (s, 9 H) 1.99-2.23 (m, 1 H) 3.98 (dd, J=14.05, 3.51 Hz, 1 H) 4.47-4.71 (m, 2 H) 7.47 (s, 1 H) 9.17 (s, 1 H). LCMS (ESI) 383 (M+H).

후처리

  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

출처 및 근거

ORD 기록
ord-9dbab369cadc42f0a3e9db4238476d74
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08691830B2

반응 노트

불러오는 중…