Triethylamine → 4'-Cyano-6-methyl-biphenyl-3-carboxylic acid [4-(morpholine-4-sulfonyl)-phenyl]-amide

HRID 1924798

Reaction equation

HRID 1924798 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:14]([CH3:15])=[CH:13][CH:12]=[C:11]([C:16]([OH:18])=O)[CH:10]=2)=[CH:5][CH:4]=1)#[N:2].C(Cl)(=O)C(Cl)=O.[N:25]1([S:31]([C:34]2[CH:39]=[CH:38][C:37]([NH2:40])=[CH:36][CH:35]=2)(=[O:33])=[O:32])[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1.C(N(CC)CC)C>C(Cl)Cl.CN(C=O)C>[N:25]1([S:31]([C:34]2[CH:35]=[CH:36][C:37]([NH:40][C:16]([C:11]3[CH:10]=[C:9]([C:6]4[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:8][CH:7]=4)[C:14]([CH3:15])=[CH:13][CH:12]=3)=[O:18])=[CH:38][CH:39]=2)(=[O:33])=[O:32])[CH2:26][CH2:27][O:28][CH2:29][CH2:30]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 2107944-(Morpholinosulfonyl)anilineHCID 594367094'-Cyano-6-methyl-biphenyl-3-carboxylic acid

Product 1

HCID 251244404'-Cyano-6-methyl-biphenyl-3-carboxylic acid [4-(morpholine-4-sulfonyl)-phenyl]-amide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of 4′-cyano-6-methyl-biphenyl-3-carboxylic acid 3 (40 mg, 0.17 mmol) in anhydrous methylene chloride (5 ml) is added 2 drops of DMF. Then oxalyl chloride (32 mg, 22 μl, 0.25 mmol) is added. The mixture is stirred at ambient temperature until it turns clear. After that, it is concentrated, re-dissolved in anhydrous methylene chloride (3 ml), and added to a solution of 4-(morpholine-4-sulfonyl)-phenylamine (61 mg, 0.25 mmol) and triethylamine (34 mg, 47 t, 0.33 mmol) in methylene chloride (2 ml). The mixture is stirred for 2 hours, concentrated and the residue is purified by preparative mass triggered HPLC (C1-8 column, eluted with CH3CN—H2O containing 0.05% TFA) to give 4′-cyano-6-methyl-biphenyl-3-carboxylic acid [4-(morpholine-4-sulfonyl)-phenyl]-amide: 1H NMR (DMSO-d6) δ 10.64 (s, 1 H), 8.07 (d, 2 H, J=8.8 Hz), 7.97 (d, 2 H, J=8.4 Hz), 7.95 (d, 1 H, J=8.8 Hz), 7.89 (s, 1 H), 7.43 (d, 2 H, J=8.4 Hz), 7.67 (d, 2 H, J=8.8 Hz), 7.53 (d, 2 H, J=8.8 Hz), 3.63 (m, 4 H), 2.84 (m, 4 H) 2.32 (s, 3 H); LC-MS m/z: 462.1 (M+1).

Workup

  1. concentrationAfter that, it is concentrated
  2. dissolutionre-dissolved in anhydrous methylene chloride (3 ml)
  3. stirringThe mixture is stirred for 2 hours
  4. concentrationconcentrated
  5. customthe residue is purified by preparative mass
  6. washHPLC (C1-8 column, eluted with CH3CN—H2O containing 0.05% TFA)

Sources & evidence

ORD record
ord-0d17aa22a9584b3ca9feff3433d9dbd1
Source dataset
uspto-grants-2012_05
Patent number
US08178563B2

Linked notes

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