Ammonium Chloride → cis 3-(5-amino-1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridine-4-ylamino)-cyclohexanecarbonitrile

HRID 1257719Notes

Reaction equation

HRID 1257719 reaction equation
[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([N+:28]([O-])=O)[C:18]([NH:19][C@@H:20]4[CH2:25][CH2:24][CH2:23][C@H:22]([C:26]#[N:27])[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.[Cl-].[NH4+]>CO.O.[Fe]>[NH2:28][C:17]1[C:18]([NH:19][C@@H:20]2[CH2:25][CH2:24][CH2:23][C@H:22]([C:26]#[N:27])[CH2:21]2)=[C:13]2[CH:12]=[CH:11][N:10]([S:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)(=[O:9])=[O:8])[C:14]2=[N:15][CH:16]=1

Participants

5

Reactant 2

HCID 25517Ammonium ChlorideHCID 86656736cis 3-(1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridine-4-ylamino)cyclohexanecarbonitrile

Product 1

HCID 86656737cis 3-(5-amino-1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridine-4-ylamino)-cyclohexanecarbonitrileYield 81%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 22242641Methanol--water (1/1)Solvent

Conditions

Temperature
85 °C

Procedure

A mixture of cis 3-(1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridine-4-ylamino)cyclohexanecarbonitrile (730 mg, 1.72 mmol), ammonium chloride (552 mg, 10.3 mmol) and iron powder (384 mg, 6.88 mmol) in methanol/H2O (3:1, v/v) was heated at 85° C. for 3.5 hr. The cooled reaction mixture was filtered through celite and the filtrate concentrated under vacuum. The residue was dissolved in DCM, washed with saturated sodium bicarbonate solution and brine, dried over sodium sulfate and concentrated under vacuum to a foam. The resulting residue was purified by column chromatography on silica gel (gradient: 0 to 4% MeOH in DCM) to afford 0.55 g (81%) of cis 3-(5-amino-1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridine-4-ylamino)-cyclohexanecarbonitrile. LCMS (Method H, ESI): RT=2.45 min, m+H=396.1; 1H NMR (400 MHz, DMSO) δ: 8.01 (d, 2H), 7.66 (m, 1H), 7.57 (m, 3H), 7.49 (d, 1H), 6.75 (d, 1H), 5.14 (d, 1H), 4.36 (s, 2H), 3.72 (m, 1H), 2.98 (m, 1H), 2.22 (m, 1H), 2.01-1.84 (m, 2H), 1.75 (m, 1H), 1.53-1.36 (m, 3H), 1.22 (d, 1H).

Workup

  1. customThe cooled reaction mixture
  2. filtrationwas filtered through celite
  3. concentrationthe filtrate concentrated under vacuum
  4. dissolutionThe residue was dissolved in DCM
  5. washwashed with saturated sodium bicarbonate solution and brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under vacuum to a foam
  8. customThe resulting residue was purified by column chromatography on silica gel (gradient: 0 to 4% MeOH in DCM)

Sources & evidence

ORD record
ord-513a01d2317d4cc99f772b285fca298f
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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