Ammonium Chloride → HCID 178511416, compound

HRID 1257704Notes

Reaction equation

HRID 1257704 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][C@H:20]4[CH2:25][CH2:24][C@H:23]([O: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.[Cl-].[NH4+]>C(O)C.O.[Fe]>[NH2:30][C:17]1[C:18]([NH:19][C@H:20]2[CH2:21][CH2:22][C@H:23]([O: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

6

Reactant 2

HCID 25517Ammonium ChlorideHCID 178511417HCID 178511417, compound

Product 1

HCID 178511416HCID 178511416, compoundYield 91.6%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of trans [4-(1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-cyclohexyloxy]-acetonitrile (350 mg, 770 μmol) in a mixture of ethanol (2.5 mL) and water (800 μL) was treated with ammonium chloride (250 mg, 4.60 mmol) and iron powder (170 mg, 3.10 mmol) and heated at 80° C. for 90 minutes. The reaction mixture was hot filtered through Celite® washing several times with ethanol/water. The filtrate was concentrated under vacuum, the residue diluted with water and extracted in to DCM (3×). The combined organic extracts were dried over sodium sulfate and concentrated under vacuum. The iron filter cake was stirred in 20% methanol in DCM, filtered and repeated until no further product was extracted. The combined filtrates were washed with water and the phases separated. The aqueous phase was extracted with DCM (2×). The combined organic extracts were washed with brine, dried over sodium sulfate, concentrated under vacuum and combined with the material isolated above to afford 300 mg (91%) of trans [4-(5-amino-1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-cyclohexyloxy]-acetonitrile as a yellow solid. LCMS (Method Q, ESI): RT=2.76 min, m+H=426.1; 1H NMR (400 MHz, CDCl3) δ: 8.14 (m, 2H), 7.83 (s, 1H), 7.53 (t, 1H), 7.49 (d, 1H), 7.45 (t, 2H), 6.52 (d, 1H), 4.72 (d, 1H), 4.30 (s, 2H), 3.73 (m, 1H), 3.58 (m, 1H), 2.80 (br s, 2H), 2.16 (m, 4H), 1.48 (m, 2H), 1.33 (m, 2H).

Workup

  1. filtrationThe reaction mixture was hot filtered through Celite®
  2. washwashing several times with ethanol/water
  3. concentrationThe filtrate was concentrated under vacuum
  4. additionthe residue diluted with water
  5. extractionextracted in to DCM (3×)
  6. dry with materialThe combined organic extracts were dried over sodium sulfate
  7. concentrationconcentrated under vacuum
  8. filtrationThe iron filter cake
  9. filtrationfiltered
  10. extractionwas extracted
  11. washThe combined filtrates were washed with water
  12. customthe phases separated
  13. extractionThe aqueous phase was extracted with DCM (2×)
  14. washThe combined organic extracts were washed with brine
  15. dry with materialdried over sodium sulfate
  16. concentrationconcentrated under vacuum
  17. customisolated above

Sources & evidence

ORD record
ord-aa2ceac6462340239043c53c35bd9d42
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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