Pyridine → n-((1s,2r)-2-{[(Cyanomethyl)amino]carbonyl}cyclohexyl)-4-{[(pyridin-4-ylmethyl)amino]sulfonyl}benzamide

HRID 1593984Notes

Reaction equation

HRID 1593984 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[C:8]([NH:10][CH2:11][C:12]#[N:13])=[O:9].N1C=CC=CC=1.F[S:21]([C:24]1[CH:32]=[CH:31][C:27]([C:28](Cl)=[O:29])=[CH:26][CH:25]=1)(=[O:23])=[O:22].C(CNC([C@@H]1CCCC[C@@H]1NC(=O)C1C=CC(F)=CC=1)=O)#N.C(N(CC)CC)C.[N:62]1[CH:67]=[CH:66][C:65]([CH2:68][NH2:69])=[CH:64][CH:63]=1>ClCCl.CO>[C:12]([CH2:11][NH:10][C:8]([C@@H:3]1[CH2:4][CH2:5][CH2:6][CH2:7][C@@H:2]1[NH:1][C:28](=[O:29])[C:27]1[CH:31]=[CH:32][C:24]([S:21]([NH:69][CH2:68][C:65]2[CH:66]=[CH:67][N:62]=[CH:63][CH:64]=2)(=[O:23])=[O:22])=[CH:25][CH:26]=1)=[O:9])#[N:13]

Participants

9

Reactant 6

HCID 1049PyridineHCID 8471TriethylamineHCID 773174-PyridinemethanamineHCID 976284-(Fluorosulfonyl)benzoyl chlorideHCID 60098554(1r,2s)-2-Amino-n-(cyanomethyl)cyclohexanecarboxamideHCID 87823520n-((1s,2r)-2-{[(Cyanomethyl)amino]carbonyl}cyclohexyl)-4fluorobenzamide

Product 1

HCID 59000826n-((1s,2r)-2-{[(Cyanomethyl)amino]carbonyl}cyclohexyl)-4-{[(pyridin-4-ylmethyl)amino]sulfonyl}benzamideYield 48%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 912 mg (5.03 mmol) (1R,2S)-2-amino-N-(cyanomethyl)cyclohexanecarboxamide (prepared according to method C) and 895 uL (11.07 mmol) pyridine dissolved in 10 mL dichloromethane was added 1.12 g (5.03 mmol) 4-(fluorosulfonyl)benzoyl chloride. The mixture was stirred for 30 minutes, partitioned between dichloromethane and 1 N HCl, dried over magnesium sulfate and concentrated to provide 1.54 g (84% yield) of crude product, pure by 1H NMR. To a mixture of 100 mg (0.272 mmol) of the above crude N-((1S,2R)-2-{[(cyanomethyl)amino]carbonyl}cyclohexyl)-4fluorobenzamide and 114 uL (0.817 mmol) triethylamine dissolved in 5 mL dichloromethane was added 88 mg (0.817 mmol) 4-picolylamine. The mixture was stirred at room temperature for 3 days, partitioned between ethyl acetate and water, dried over magnesium sulfate and concentrated. Column -chromatography, eluting with 20:1 dichloromethane:methanol provided 59 mg (48% yield) of N-((1S,2R)-2-{[(cyanomethyl)amino]carbonyl}cyclohexyl)-4-{[(pyridin-4-ylmethyl)amino]sulfonyl}benzamide, which was used in the preparation of compound 58 of Table 1.

Workup

  1. custompartitioned between dichloromethane and 1 N HCl
  2. dry with materialdried over magnesium sulfate
  3. concentrationconcentrated
  4. customto provide 1.54 g (84% yield) of crude product
  5. stirringThe mixture was stirred at room temperature for 3 days
  6. custompartitioned between ethyl acetate and water
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated
  9. washColumn -chromatography, eluting with 20:1 dichloromethane

Sources & evidence

ORD record
ord-850ca0d746534b32a5198ac08db98a71
Source dataset
uspto-grants-2007_11
Patent number
US07300934B2

Reaction notes

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