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

HRID 1257614Notes

Reaction equation

HRID 1257614 reaction equation
[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([N+:31]([O-])=O)[C:18]([NH:19][CH:20]4[CH2:25][CH2:24][N:23]([CH:26]([CH3:30])[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>[NH2:31][C:17]1[C:18]([NH:19][CH:20]2[CH2:21][CH2:22][N:23]([CH:26]([CH3:30])[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 673427783-[4-(1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-piperidin-1-yl]-butyronitrile

Product 1

HCID 673436313-[4-(5-amino-1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-piperidin-1-yl]-butyronitrileYield 61.6%

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]-butyronitrile (11.3 g, 24.1 mmol) and palladium on carbon (3.2 g, 10%, wet, Degussa, E101 NE/W) in EtOAc (150 ml) was stirred under a hydrogen atmosphere (2-3 balloons) at 50° C. for 14 h. The reaction mixture was cooled to 25° C. then was filtered through Celite and the Celite was 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 8% CH3OH in CH2Cl2) afforded 3-[4-(5-amino-1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-piperidin-1-yl]-butyronitrile (6.51 g, 61%) as a grey foam. TLC: 5% CH3OH in CH2Cl2, Rf=0.40; 1H NMR (400 MHz, CDCl3) δ 8.12 (d, J=7.8 Hz, 2H), 7.81 (s, 1H), 7.56-7.49 (m, 1H), 7.48-7.39 (m, 3H), 6.52 (d, J=4.2 Hz, 1H), 4.74 (d, J=8.5 Hz, 1H), 3.75-3.63 (m, 1H), 3.13-3.00 (m, 1H), 2.90-2.69 (m, 3H), 2.51 (dd, J=16.7, 6.3 Hz, 1H), 2.45-2.32 (m, 3H), 2.06 (d, J=10.9 Hz, 2H), 1.61-1.46 (m, 2H), 1.19 (d, J=6.7 Hz, 3H).

Workup

  1. temperatureThe reaction mixture was cooled to 25° C.
  2. filtrationthen was filtered through Celite
  3. washthe Celite was 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 8% CH3OH in CH2Cl2)

Sources & evidence

ORD record
ord-cfee04d3996842b29e7d515ce59703d9
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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