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

HRID 2362282ノート

反応式

HRID 2362282 の反応式
[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]

参加物

9

反応物 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

生成物 1

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

試薬・触媒・溶媒 5

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒2 回HCID 21899381Acetic acid--water (1/1)溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-9dbab369cadc42f0a3e9db4238476d74
出典データセット
uspto-grants-2014_04
特許番号
US08691830B2

反応ノート

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