1H-imidazole-2-carbaldehyde → 2-[5-chloro-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridin-3-yl]-5-fluoro-N-[(3S)-1-(1H-imidazol-2-ylmethyl)-3-piperidyl]pyrimidin-4-amine

HRID 74868

Reaction equation

HRID 74868 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][C@H:18]4[CH2:23][CH2:22][CH2:21][NH:20][CH2:19]4)[C:14]([F:24])=[CH:13][N:12]=3)=[CH:9][N:8]([S:25]([C:28]3[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=3)(=[O:27])=[O:26])[C:5]2=[N:6][CH:7]=1.[NH:35]1[CH:39]=[CH:38][N:37]=[C:36]1[CH:40]=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C(O)(=O)C.C([O-])(O)=O.[Na+]>[NH:35]1[CH:39]=[CH:38][N:37]=[C:36]1[CH2:40][N:20]1[CH2:21][CH2:22][CH2:23][C@H:18]([NH:17][C:15]2[C:14]([F:24])=[CH:13][N:12]=[C:11]([C:10]3[C:4]4[C:5](=[N:6][CH:7]=[C:2]([Cl:1])[CH:3]=4)[N:8]([S:25]([C:28]4[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=4)(=[O:27])=[O:26])[CH:9]=3)[N:16]=2)[CH2:19]1

Participants

7

Reactant 3

HCID 249551H-imidazole-2-carbaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 672851192-[5-chloro-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridin-3-yl]-5-fluoro-N-[(3S)-3-piperidyl]pyrimidin-4-amine2×

Product 1

HCID 672877632-[5-chloro-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridin-3-yl]-5-fluoro-N-[(3S)-1-(1H-imidazol-2-ylmethyl)-3-piperidyl]pyrimidin-4-amine

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 111,2-DichloroethaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 2-[5-chloro-1-(p-tolylsulfonyl)pyrrolo[5,4-b]pyridin-3-yl]-5-fluoro-N-[(3S)-3-piperidyl]pyrimidin-4-amine, 1c, (0.16 g, 0.32 mmol) in 1,2-dichloroethane (2 mL) was added 1H-imidazole-2-carbaldehyde (0.03 g, 0.36 mmol) followed by 2 drops of acetic acid and Na(OAc)3BH (0.10 g, 0.49 mmol). The reaction mixture was heated at 60° C. for 18 h. The mixture was cooled to room temperature and diluted with aqueous saturated NaHCO3 solution. The aqueous phase was extracted twice with EtOAc. The combined organic phases were dried (MgSO4), filtered and concentrated in vacuo. The crude residue was purified via silica gel chromatography (0-20% MeOH/CH2Cl2) to afford the product, 4a.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionThe aqueous phase was extracted twice with EtOAc
  3. dry with materialThe combined organic phases were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude residue was purified via silica gel chromatography (0-20% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-d52e158efc06453da4cc711ff06912c4
Source dataset
uspto-grants-2014_09
Patent number
US08829007B2

Linked notes

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