Water → HCID 178511025, compound

HRID 1257714Notes

Reaction equation

HRID 1257714 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]([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.O.[Cl-].[NH4+]>C(O)C.C(Cl)Cl.[Fe]>[NH2:30][C:17]1[C:18]([NH:19][C@H:20]2[CH2:21][CH2:22][C@H: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:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)(=[O:9])=[O:8])[C:14]2=[N:15][CH:16]=1

Participants

7

Reactant 3

HCID 962WaterHCID 25517Ammonium ChlorideHCID 178511027HCID 178511027, compound

Product 1

HCID 178511025HCID 178511025, compoundYield 83%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of trans 3-[4-(1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-cyclohexyl]-propionitrile (3.83 g, 8.50 mmol) in ethanol (28.5 mL, IMS grade) was treated with water (9.5 mL) followed by ammonium chloride (2.71 g, 50.7 mmol) and iron powder (1.89 g, 33.8 mmol) and the mixture was heated to 80° C. for 45 minutes. The solid was filtered and washed with ethanol (IMS grade). The filter cake was extracted repeatedly with DCM. The DCM extracts were washed with water and the aqueous layer was back-extracted with DCM (×2). The combined DCM extracts were washed with brine, dried with sodium sulfate and concentrated under vacuum to give 2.08 g of crude product. The filtered cake, from above, was extracted repeatedly with 2M NH3 in MeOH. The washings were concentrated under vacuum and worked up to provide a further 190 mg of crude product. The remaining filter cake was stirred with DCM (35 mL) and the DCM decanted off, and then 20% [2N NH3 in MeOH] in DCM. The combined chlorinated extracts were filtered through Celite® to remove traces of iron residue and concentrated under vacuum to give a third batch of crude product (0.66 g). The three batches of crude product were dissolved in DCM, combined and concentrated under vacuum to give 2.97 g (83%) of trans 3-[4-(5-amino-1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-cyclohexyl]-propionitrile as a pale brown solid that was used in the next step without further purification. 1H NMR (400 MHz, DMSO) δ: 8.01 (d, 2H), 7.66 (t, 1H), 7.57 (t, 2H), 7.54 (s, 1H), 7.46 (d, 1H), 6.66 (d, 1H), 5.10 (d, 1H), 4.33 (s, 2H), 3.68-3.56 (m, 1H), 2.01-1.91 (m, 2H), 1.81-1.72 (m, 2H), 1.50 (q, 2H), 1.38-1.19 (m, 3H), 1.17-1.04 (m, 2H) plus 2H obscured by solvent peak.

Workup

  1. filtrationThe solid was filtered
  2. washwashed with ethanol (IMS grade)
  3. extractionThe filter cake was extracted repeatedly with DCM
  4. washThe DCM extracts were washed with water
  5. extractionthe aqueous layer was back-extracted with DCM (×2)
  6. washThe combined DCM extracts were washed with brine
  7. dry with materialdried with sodium sulfate
  8. concentrationconcentrated under vacuum
  9. customto give 2.08 g of crude product
  10. extractionThe filtered cake, from above, was extracted repeatedly with 2M NH3 in MeOH
  11. concentrationThe washings were concentrated under vacuum
  12. customto provide a further 190 mg of crude product
  13. filtrationThe remaining filter cake
  14. customthe DCM decanted off
  15. filtrationwere filtered through Celite®
  16. customto remove traces of iron residue
  17. concentrationconcentrated under vacuum
  18. customto give a third batch of crude product (0.66 g)
  19. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-10ed18b18a6e4eeabc9f46eecbbf37f7
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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