Diisopropylethylamine → 1,1-Dimethylethyl {3-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]phenyl}carbamate

HRID 1675681노트

반응식

HRID 1675681 반응식
[NH2:1][CH2:2][C:3]1[C:8]([CH2:9][CH3:10])=[N:7][C:6]2[N:11]([CH2:14][CH3:15])[N:12]=[CH:13][C:5]=2[C:4]=1[NH:16][CH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1.[CH3:23][C:24]([O:27][C:28]([NH:30][C:31]1[CH:32]=[C:33]([CH:37]=[CH:38][CH:39]=1)[C:34](O)=[O:35])=[O:29])([CH3:26])[CH3:25].C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1>CN(C)C=O>[CH2:14]([N:11]1[C:6]2=[N:7][C:8]([CH2:9][CH3:10])=[C:3]([CH2:2][NH:1][C:34]([C:33]3[CH:32]=[C:31]([NH:30][C:28](=[O:29])[O:27][C:24]([CH3:25])([CH3:23])[CH3:26])[CH:39]=[CH:38][CH:37]=3)=[O:35])[C:4]([NH:16][CH:17]3[CH2:18][CH2:19][O:20][CH2:21][CH2:22]3)=[C:5]2[CH:13]=[N:12]1)[CH3:15]

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 8541623-(((Tert-butoxy)carbonyl)amino)benzoic acidHCID 2724699PyBOP2회HCID 596832145-(Aminomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine

생성물 1

HCID 580247571,1-Dimethylethyl {3-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]phenyl}carbamate수율 44.5%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A mixture of Intermediate 7 (250 mg, 0,83 mmol) and 3-({[(1,1-dimethylethyl)oxy]carbonyl}amino)benzoic acid (196 mg, 0.83 mmol, e.g. available from Fluka) in N,N-dimethylformamide (4 ml) was treated with N,N-diisopropylethylamine (0.569 ml, 3.3 mmol) and (1H-1,2,3-benzotriazol-1-yloxy)(tri-1-pyrrolidinyl)phosphonium hexafluorophosphate (472 mg, 0.91 mmol) and allowed to stir at room temperature for 4 hours. An additional portion of (1H-1,2,3-benzotriazol-1-yloxy)(tri-1-pyrrolidinyl)phosphonium hexafluorophosphate (0.5 equivalents, 0.41 mmol) was added and the mixture stirred for an additional hour. The solvent was evaporated and the residue partitioned between ethyl acetate (50 ml) and aqueous sodium bicarbonate solution (50 ml); saturated sodium chloride solution was added and the layers allowed to separate overnight. The aqueous layer was further extracted with ethyl acetate (50 ml), and the organic fractions collected, dried (Na2SO4) and evaporated; however the residue contained very little product. A white solid was filtered off from the aqueous layer and dried to give the title compound (193 mg). LCMS showed MH+=523; TRET=2.99 min.

후처리

  1. stirringthe mixture stirred for an additional hour
  2. customThe solvent was evaporated
  3. customthe residue partitioned between ethyl acetate (50 ml) and aqueous sodium bicarbonate solution (50 ml)
  4. additionsaturated sodium chloride solution was added
  5. customto separate overnight
  6. extractionThe aqueous layer was further extracted with ethyl acetate (50 ml)
  7. customthe organic fractions collected
  8. dry with materialdried (Na2SO4)
  9. customevaporated
  10. filtrationA white solid was filtered off from the aqueous layer
  11. customdried

출처 및 근거

ORD 기록
ord-edf94aaebb0045558df482d29116b230
출처 데이터셋
uspto-grants-2011_08
특허 번호
US08003663B2

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