Diisopropylethylamine → 4-{1-benzenesulfonyl-5-[2-(3-methyl-isoxazol-4-yl)-acetylamino]-1H-pyrrolo[2,3-b]pyridin-4-ylamino}-piperidine-1-carboxylic acid tert-butyl ester

HRID 1257606Notes

Reaction equation

HRID 1257606 reaction equation
[CH3:1][C:2]1[C:6]([CH2:7][C:8]([OH:10])=O)=[CH:5][O:4][N:3]=1.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:44]([O:48][C:49]([N:51]1[CH2:56][CH2:55][CH:54]([NH:57][C:58]2[C:63]([N+:64]([O-])=O)=[CH:62][N:61]=[C:60]3[N:67]([S:70]([C:73]4[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=4)(=[O:72])=[O:71])[CH:68]=[CH:69][C:59]=23)[CH2:53][CH2:52]1)=[O:50])([CH3:47])([CH3:46])[CH3:45].C([O-])(O)=O.[Na+]>CN(C=O)C.C(Cl)Cl>[C:44]([O:48][C:49]([N:51]1[CH2:52][CH2:53][CH:54]([NH:57][C:58]2[C:63]([NH:64][C:8](=[O:10])[CH2:7][C:6]3[C:2]([CH3:1])=[N:3][O:4][CH:5]=3)=[CH:62][N:61]=[C:60]3[N:67]([S:70]([C:73]4[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=4)(=[O:71])=[O:72])[CH:68]=[CH:69][C:59]=23)[CH2:55][CH2:56]1)=[O:50])([CH3:47])([CH3:45])[CH3:46]

Participants

8

Reactant 5

HCID 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 536960533-Methyl-4-isoxazoleacetic acidHCID 673440274-(1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridine-4-ylamino)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 673461024-{1-benzenesulfonyl-5-[2-(3-methyl-isoxazol-4-yl)-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

2-(3-Methylisoxazol-4-yl)acetic acid (0.223 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-yl amino)-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-(3-methyl-isoxazol-4-yl)-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=595.4. 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-8a2af02fc7b64b54bfaa92d749843509
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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