Dichloromethane → N-(3-{3-[4-(1-aminocyclobutyl)phenyl]-2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-5-yl}phenyl)-2-hydroxy-2-methylpropanamide hydrochloride

HRID 1914010Notes

Reaction equation

HRID 1914010 reaction equation
[NH2:1][C:2]1[C:7]([C:8]2[N:29]([C:30]3[CH:35]=[CH:34][C:33]([C:36]4([NH:40]C(=O)OC(C)(C)C)[CH2:39][CH2:38][CH2:37]4)=[CH:32][CH:31]=3)[C:11]3=[N:12][C:13]([C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([NH:22][C:23](=[O:28])[C:24]([OH:27])([CH3:26])[CH3:25])[CH:17]=4)=[CH:14][CH:15]=[C:10]3[N:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.FC(F)(F)C(O)=O.[Cl:55]CCl>>[ClH:55].[NH2:40][C:36]1([C:33]2[CH:34]=[CH:35][C:30]([N:29]3[C:11]4=[N:12][C:13]([C:16]5[CH:17]=[C:18]([NH:22][C:23](=[O:28])[C:24]([OH:27])([CH3:26])[CH3:25])[CH:19]=[CH:20][CH:21]=5)=[CH:14][CH:15]=[C:10]4[N:9]=[C:8]3[C:7]3[C:2]([NH2:1])=[N:3][CH:4]=[CH:5][CH:6]=3)=[CH:31][CH:32]=2)[CH2:37][CH2:38][CH2:39]1

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 71142505tert-butyl (1-{4-[2-(2-aminopyridin-3-yl)-5-{3-[(2-hydroxy-2-methylpropanoyl)amino]phenyl}-3H-imidazo[4,5-b]pyridin-3-yl]phenyl}cyclobutyl)carbamate

Product 1

HCID 71138553N-(3-{3-[4-(1-aminocyclobutyl)phenyl]-2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-5-yl}phenyl)-2-hydroxy-2-methylpropanamide hydrochloride

Procedure

To a solution of tert-butyl (1-{4-[2-(2-aminopyridin-3-yl)-5-{3-[(2-hydroxy-2-methylpropanoyl)amino]phenyl}-3H-imidazo[4,5-b]pyridin-3-yl]phenyl}cyclobutyl)carbamate (20 mg) in dichloromethane (3 mL) was added trifluoroacetic acid (0.6 mL) dropwise at room temperature. After being stirred at the same temperature for 1 h, the reaction mixture was concentrated under reduced pressure. Dichloromethane (5 mL) and MP-carbonate (Argonaout technologies 2.91 mmol/g, 200 mg) were added. The mixture was stayed for 30 min. with occasional shaking then filtered. The filtrate was concentrated under reduced pressure. To a solution of the residue in dichloromethane (5 mL) and methanol (0.5 mL) was added hydrogen chloride in ethyl acetate (4 M, 0.04 mL) at room temperature. After being stirred for 10 min., the mixture was concentrated under reduced pressure. The resulting solid was suspended with ethyl acetate and filtered to give the product (15 mg).

Workup

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. additionDichloromethane (5 mL) and MP-carbonate (Argonaout technologies 2.91 mmol/g, 200 mg) were added
  3. waitThe mixture was stayed for 30 min.
  4. stirringwith occasional shaking
  5. filtrationthen filtered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. additionTo a solution of the residue in dichloromethane (5 mL) and methanol (0.5 mL) was added hydrogen chloride in ethyl acetate (4 M, 0.04 mL) at room temperature
  8. stirringAfter being stirred for 10 min.
  9. concentrationthe mixture was concentrated under reduced pressure
  10. filtrationfiltered

Sources & evidence

ORD record
ord-bcfd72deb30e4a7a95036786e5758102
Source dataset
uspto-grants-2013_12
Patent number
US08609688B2

Reaction notes

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