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 1675681Notes

Reaction equation

HRID 1675681 reaction equation
[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]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 8541623-(((Tert-butoxy)carbonyl)amino)benzoic acidHCID 2724699PyBOP2×HCID 596832145-(Aminomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine

Product 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}carbamateYield 44.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-edf94aaebb0045558df482d29116b230
Source dataset
uspto-grants-2011_08
Patent number
US08003663B2

Reaction notes

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