Acetone → N-(4-(4-(3-(isopropylamino)propanoyl)piperazin-1-yl)-5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide

HRID 79624Notes

Reaction equation

HRID 79624 reaction equation
[NH2:1][CH2:2][CH2:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12]2[C:17]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:16][N:15]=[C:14]3[NH:24][CH:25]=[C:26]([NH:27][C:28](=[O:35])[C:29]4[CH:34]=[CH:33][CH:32]=[N:31][CH:30]=4)[C:13]=23)[CH2:8][CH2:7]1)=[O:5].[CH3:36][C:37]([CH3:39])=O.CCN(C(C)C)C(C)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])([O-])=O.[Na+].[Na+].Cl>C(Cl)Cl.CCOCC.CO.CN(C=O)C.ClCCCl>[CH:37]([NH:1][CH2:2][CH2:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12]2[C:17]([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)=[CH:16][N:15]=[C:14]3[NH:24][CH:25]=[C:26]([NH:27][C:28](=[O:35])[C:29]4[CH:34]=[CH:33][CH:32]=[N:31][CH:30]=4)[C:13]=23)[CH2:8][CH2:7]1)=[O:5])([CH3:39])[CH3:36]

Participants

12

Reactant 6

HCID 180AcetoneHCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 44198253HCID 44198253, compound

Product 1

HCID 44198256N-(4-(4-(3-(isopropylamino)propanoyl)piperazin-1-yl)-5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamideYield 7.5%

Reagents, catalysts & solvents 5

HCID 111,2-DichloroethaneSolventHCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

N-(4-(4-(3-Aminopropanoyl)piperazin-1-yl)-5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide (0.015 g, 0.026 mmol, see Example 65) and acetone (0.0150 g, 0.259 mmol) were placed in 1:1 DCE:DMF (2 mL). DIEA (d 0.742; 0.0226 mL, 0.130 mmol) was then added, followed by the addition of NaBH(OAc)3 (0.0110 g, 0.0518 mmol). The reaction was then stirred for 30 minutes, and poured into Na2CO3 and extracted into DCM. The organic fractions were combined, dried, filtered and concentrated. The residue was purified by reverse phase HPLC to give the product. The product was then dissolved in minimal DCM and MeOH and added to a stirring solution of 1M HCl in ether. The resulting solid was collected to give N-(4-(4-(3-(isopropylamino)propanoyl)piperazin-1-yl)-5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide (0.001 g, 6.2% yield) as the trihydrochloride salt. MS APCI (+) m/z 512 detected.

Workup

  1. extractionextracted into DCM
  2. customdried
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by reverse phase HPLC
  6. customto give the product
  7. customThe resulting solid was collected

Sources & evidence

ORD record
ord-9e772b7f62804d71aba559675c85aea7
Source dataset
uspto-grants-2014_09
Patent number
US08841304B2

Reaction notes

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