Ammonium Chloride → 3-amino-5-cyano-6-ethoxy-N-((1-((2-(pyridin-2-yl)thiazol-5-yl)methyl)piperidin-4-yl)methyl)picolinamide

HRID 2407840Notes

Reaction equation

HRID 2407840 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([N+:34]([O-])=O)[C:6]([C:12]([NH:14][CH2:15][CH:16]2[CH2:21][CH2:20][N:19]([CH2:22][C:23]3[S:27][C:26]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=4)=[N:25][CH:24]=3)[CH2:18][CH2:17]2)=[O:13])=[N:7][C:8]=1[O:9][CH2:10][CH3:11])#[N:2].[Cl-].[NH4+]>O1CCCC1.[Zn]>[NH2:34][C:5]1[C:6]([C:12]([NH:14][CH2:15][CH:16]2[CH2:21][CH2:20][N:19]([CH2:22][C:23]3[S:27][C:26]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=4)=[N:25][CH:24]=3)[CH2:18][CH2:17]2)=[O:13])=[N:7][C:8]([O:9][CH2:10][CH3:11])=[C:3]([C:1]#[N:2])[CH:4]=1

Participants

5

Reactant 2

HCID 25517Ammonium ChlorideHCID 585042275-cyano-6-ethoxy-3-nitro-N-((1-((2-(pyridin-2-yl)thiazol-5-yl)methyl)piperidin-4-yl)methyl)picolinamide

Product 1

HCID 585040373-amino-5-cyano-6-ethoxy-N-((1-((2-(pyridin-2-yl)thiazol-5-yl)methyl)piperidin-4-yl)methyl)picolinamideYield 44.3%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of the compound prepared in Example 448 (48 mg) in tetrahydrofuran (1 mL) at ambient temperature was added zinc dust (120 mg), and to the resulting stirred mixture added saturated ammonium chloride (0.5 mL). The resulting mixture was stirred at ambient temperature for 17 hours. The reaction mixture was diluted with tetrahydrofuran (5 mL) and filtered through a glass microfibre filter. The flask and filter were rinsed with additional tetrahydrofuran. The combined filtrate and rinses were concentrated to remove most of the tetrahydrofuran, and the residue was partitioned between ethyl acetate and water, with addition of 10% sodium carbonate. The organic layer was dried over sodium sulfate and concentrated. The residue was purified by chromatography on silica gel, eluting with 99/1 chloroform/methanol to provide the title compound (20 mg) with the following physical data. 1H NMR (CDCl3): δ 8.60 (d, J=4.4 Hz, 1H), 8.15 (d, J=8.0 Hz, 1H), 7.79 (m, 2H), 7.68 (s, 1H), 7.32 (m, 2H), 5.77 (broad s, 2H), 4.35 (q, J=7.2 Hz, 2H), 3.80 (broad s, 2H), 3.33 (t, J=6.8 Hz, 2H), 2.99 (d, J=10.8 Hz, 2H), 2.11 (t, J=10.8 Hz, 2H), 1.76 (d, J=12.0 Hz, 2H), 1.60 (broad s, 1H), 1.41 (m, 5H);

Workup

  1. stirringThe resulting mixture was stirred at ambient temperature for 17 hours
  2. filtrationfiltered through a glass microfibre
  3. filtrationfilter
  4. filtrationThe flask and filter
  5. washwere rinsed with additional tetrahydrofuran
  6. concentrationThe combined filtrate and rinses were concentrated
  7. customto remove most of the tetrahydrofuran
  8. customthe residue was partitioned between ethyl acetate and water, with addition of 10% sodium carbonate
  9. dry with materialThe organic layer was dried over sodium sulfate
  10. concentrationconcentrated
  11. customThe residue was purified by chromatography on silica gel
  12. washeluting with 99/1 chloroform/methanol

Sources & evidence

ORD record
ord-b57ab7bdb1d04e779b38bfe8d233d80b
Source dataset
uspto-grants-2014_08
Patent number
US08809538B2

Reaction notes

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