Cyanoacetic acid → 4-[1-benzenesulfonyl-5-(2-cyano-acetylamino)-1H-pyrrolo[2,3-b]pyridin-4-ylamino]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1257598Notes

Reaction equation

HRID 1257598 reaction equation
[C:1]([CH2:3][C:4]([OH:6])=O)#[N:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[C:40]([O:44][C:45]([N:47]1[CH2:52][CH2:51][CH:50]([NH:53][C:54]2[C:59]([N+:60]([O-])=O)=[CH:58][N:57]=[C:56]3[N:63]([S:66]([C:69]4[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=4)(=[O:68])=[O:67])[CH:64]=[CH:65][C:55]=23)[CH2:49][CH2:48]1)=[O:46])([CH3:43])([CH3:42])[CH3:41].C([O-])(O)=O.[Na+]>CN(C=O)C.C(Cl)Cl>[C:40]([O:44][C:45]([N:47]1[CH2:48][CH2:49][CH:50]([NH:53][C:54]2[C:59]([NH:60][C:4](=[O:6])[CH2:3][C:1]#[N:2])=[CH:58][N:57]=[C:56]3[N:63]([S:66]([C:69]4[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=4)(=[O:67])=[O:68])[CH:64]=[CH:65][C:55]=23)[CH2:51][CH2:52]1)=[O:46])([CH3:43])([CH3:41])[CH3:42]

Participants

8

Reactant 5

HCID 9740Cyanoacetic acidHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 673440274-(1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridine-4-ylamino)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 673425034-[1-benzenesulfonyl-5-(2-cyano-acetylamino)-1H-pyrrolo[2,3-b]pyridin-4-ylamino]-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

Cyanoacetic acid (0.134 g, 1.58 mmol), HATU (0.600 g, 1.58 mmol), and diisopropylethylamine (0.300 ml, 1.72 mmol) were added sequentially to a solution of 4-(5-amino-1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-piperidine-1-carboxylic acid tert-butyl ester (0.677 g, 1.44 mmol, prepared as described in Example 115) in a 6:1 mixture of CH2Cl2 and DMF (7 ml) at 25° C. The reaction mixture was stirred for 14 h at 25° C., then saturated NaHCO3 (7 ml) was added and the mixture was vigorously shaken by hand for 1 min. The phases were separated using a phase separation column (Biotage) and the organic layer was concentrated under reduced pressure to give crude 4-[1-benzenesulfonyl-5-(2-cyano-acetylamino)-1H-pyrrolo[2,3-b]pyridin-4-ylamino]-piperidine-1-carboxylic acid tert-butyl ester as a brown oil. LCMS (Method G, ESI): RT=0.99 min, m+H=539.3. This material was used in the next step below without additional purification or characterization.

Workup

  1. stirringthe mixture was vigorously shaken by hand for 1 min
  2. customThe phases were separated
  3. customa phase separation column (Biotage)
  4. concentrationthe organic layer was concentrated under reduced pressure

Sources & evidence

ORD record
ord-05c3d59d5f5144208e7e28e6d4707430
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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