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

HRID 1257603Notes

Reaction equation

HRID 1257603 reaction equation
[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([N+:20]([O-:22])=[O:21])[C:18](Cl)=[C:13]3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:23][CH:24]1[CH2:29][CH2:28][N:27]([CH2:30][CH2:31][C:32]#[N:33])[CH2:26][CH2:25]1.C(N(C(C)C)CC)(C)C>CC(O)C>[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([N+:20]([O-:22])=[O:21])[C:18]([NH:23][CH:24]4[CH2:29][CH2:28][N:27]([CH2:30][CH2:31][C:32]#[N:33])[CH2:26][CH2:25]4)=[C:13]3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 22562162N-(2-cyanoethyl)-4-aminopiperidineHCID 583947741-(benzenesulfonyl)-4-chloro-5-nitro-1H-pyrrolo(2,3-b)pyridine

Product 1

HCID 673457373-[4-(1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-piperidin-1-yl]-propionitrileYield 93.3%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 1-benzenesulfonyl-4-chloro-5-nitro-1H-pyrrolo[2,3-b]pyridine (15.35 g, 45.5 mmol), 3-(4-amino-piperidin-1-yl)-propionitrile (hydrochloride salt) (9.48 g, 50.0 mmol), diisopropylethylamine (24.5 ml, 141 mmol) in propan-2-ol (200 ml) was heated at 80° C. for 18 h. The mixture was cooled to 25° C. and was concentrated to approximately 40 ml volume. This material was partitioned between water (2000 ml) and CH2Cl2 (3×2000 ml). The combined organic layers were dried over MgSO4, filtered, and the filtrate was concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel (gradient: 0 to 6% CH3OH in CH2Cl2) afforded 3-[4-(1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-piperidin-1-yl]-propionitrile (19.3 g, 93% over 3 steps) as a yellow-orange foam. LCMS (Method G, ESI): RT=0.69 min, m+H=455.3. This material was used in the next step below without additional characterization.

Workup

  1. temperatureThe mixture was cooled to 25° C.
  2. concentrationwas concentrated to approximately 40 ml volume
  3. customThis material was partitioned between water (2000 ml) and CH2Cl2 (3×2000 ml)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customPurification of the residue by column chromatography on silica gel (gradient: 0 to 6% CH3OH in CH2Cl2)

Sources & evidence

ORD record
ord-2028ee8b8b8241399b50ddce3b80f2fe
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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