3-[4-(1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-piperidin-1-yl]-propionitrile → 3-[4-(5-amino-1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-piperidin-1-yl]-propionitrile

HRID 1257604Notes

Reaction equation

HRID 1257604 reaction equation
[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([N+:30]([O-])=O)[C:18]([NH:19][CH:20]4[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][C:28]#[N:29])[CH2:22][CH2:21]4)=[C:13]3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>[Pd].CCOC(C)=O>[NH2:30][C:17]1[C:18]([NH:19][CH:20]2[CH2:21][CH2:22][N:23]([CH2:26][CH2:27][C:28]#[N:29])[CH2:24][CH2:25]2)=[C:13]2[CH:12]=[CH:11][N:10]([S:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)(=[O:9])=[O:8])[C:14]2=[N:15][CH:16]=1

Participants

4

Reactant 1

HCID 673457373-[4-(1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-piperidin-1-yl]-propionitrile

Product 1

HCID 673456183-[4-(5-amino-1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-piperidin-1-yl]-propionitrileYield 753.8%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A suspension of 3-[4-(1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-piperidin-1-yl]-propionitrile (19.3 g, 4.25 mmol) and palladium on carbon (3.7 g, 10%, wet, Degussa, E101 NE/W) in EtOAc (150 ml) was stirred under a hydrogen atmosphere (2-3 balloons) at 50° C. for 24 h. The reaction mixture was cooled to 25° C. then was filtered through Celite and the Celite washed with EtOAc (2×20 ml). The filtrate and washings were concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel (gradient: 0 to 6% CH3OH in CH2Cl2) afforded 3-[4-(5-amino-1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-piperidin-1-yl]-propionitrile (13.6 g, 75%) as a grey foam. 1H NMR (400 MHz, CDCl3) δ 8.17-8.09 (m, 2H), 7.83 (s, 1H), 7.54 (t, J=7.4 Hz, 1H), 7.49-7.41 (m, 3H), 6.52 (d, J=4.2 Hz, 1H), 4.76 (d, J=8.4 Hz, 1H), 3.79-3.66 (m, 1H), 2.94-2.82 (m, 3H), 2.72 (t, J=6.9 Hz, 2H), 2.51 (t, J=6.9 Hz, 2H), 2.29 (td, J=11.5, 2.1 Hz, 2H), 2.12-2.00 (m, 2H), 1.58 (qd, J=10.9, 3.6 Hz, 2H). This material was used in the next step below without additional characterization.

Workup

  1. temperatureThe reaction mixture was cooled to 25° C.
  2. filtrationthen was filtered through Celite
  3. washthe Celite washed with EtOAc (2×20 ml)
  4. concentrationThe filtrate and washings were concentrated under reduced pressure
  5. customPurification of the residue by column chromatography on silica gel (gradient: 0 to 6% CH3OH in CH2Cl2)

Sources & evidence

ORD record
ord-1ec0d2763d2c48539e8f084a68b40aee
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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