Sodium hydride → 3'-(6-Methanesulfonylaminocarbonyl-3,3-dimethyl-1,2,3,4-tetrahydro-quinolin-2-yl)-biphenyl-4-carboxylic acid tert-butylamide

HRID 1801242Notes

Reaction equation

HRID 1801242 reaction equation
[H-].[Na+].[CH3:3][S:4]([NH2:7])(=[O:6])=[O:5].[C:8]([NH:12][C:13]([C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([CH:27]3[C:36]([CH3:38])([CH3:37])[CH2:35][C:34]4[C:29](=[CH:30][CH:31]=[C:32]([C:39](O)=[O:40])[CH:33]=4)[NH:28]3)[CH:22]=2)=[CH:17][CH:16]=1)=[O:14])([CH3:11])([CH3:10])[CH3:9].C(N1C=CN=C1)(N1C=CN=C1)=O>CN(C)C=O>[C:8]([NH:12][C:13]([C:15]1[CH:16]=[CH:17][C:18]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([CH:27]3[C:36]([CH3:38])([CH3:37])[CH2:35][C:34]4[C:29](=[CH:30][CH:31]=[C:32]([C:39]([NH:7][S:4]([CH3:3])(=[O:6])=[O:5])=[O:40])[CH:33]=4)[NH:28]3)[CH:22]=2)=[CH:19][CH:20]=1)=[O:14])([CH3:11])([CH3:9])[CH3:10]

Participants

6

Reactant 4

HCID 24758Sodium hydride2×HCID 682631,1'-CarbonyldiimidazoleHCID 72879Methanesulfonamide2×HCID 584762882-(4'-Tert-butylcarbamoyl-biphenyl-3-yl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid

Product 1

HCID 584762293'-(6-Methanesulfonylaminocarbonyl-3,3-dimethyl-1,2,3,4-tetrahydro-quinolin-2-yl)-biphenyl-4-carboxylic acid tert-butylamideYield 20%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
25 °C

Procedure

To a suspension of 60% sodium hydride (87 mg, 2.1 mmol) in N,N-dimethylformamide (1.5 mL) was added methanesulfonamide (210 mg, 2.2 mmol) at room temperature. The resulting mixture was stirred at 25° C. for 1 h. A solution of 2-(4′-tert-butylcarbamoyl-biphenyl-3-yl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid (100 mg, 0.22 mmol) and 1,1′-carbonyldiimidazole (72 mg, 0.44 mmol) in N,N-dimethylformamide (2.0 mL) was stirred at 70° C. After stirring at 70° C. for 1 h, the above suspension of methanesulfonamide and sodium hydride in N,N-dimethylformamide was added and the mixture was allowed to stir at 25° C. for 1 h. Purification by Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water) afforded 3′-(6-methanesulfonylaminocarbonyl-3,3-dimethyl-1,2,3,4-tetrahydro-quinolin-2-yl)-biphenyl-4-carboxylic acid tert-butylamide (23 mg, 20%) as a white solid: LC/MS m/e calcd for C30H35N3O4S (M+H)+: 534.70, observed: 534.1.

Workup

  1. stirringAfter stirring at 70° C. for 1 h
  2. additionwas added
  3. stirringto stir at 25° C. for 1 h
  4. customPurification by Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water)

Sources & evidence

ORD record
ord-e59b0ad6764b442db71706addc5420e4
Source dataset
uspto-grants-2013_01
Patent number
US08344137B2

Reaction notes

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