Diisopropylethylamine → 5-amino-1-[5-(5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenylcarbamoyl)-2-methyl-phenyl]-1H-pyrazole-3-carboxylic acid ethyl ester

HRID 1723953Notes

Reaction equation

HRID 1723953 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9]([NH2:11])[N:8]([C:12]2[CH:17]=[C:16]([C:18]([OH:20])=O)[CH:15]=[CH:14][C:13]=2[CH3:21])[N:7]=1)=[O:5])[CH3:2].[NH2:22][C:23]1[C:24]([O:38][CH3:39])=[C:25]([NH:33][S:34]([CH3:37])(=[O:36])=[O:35])[CH:26]=[C:27]([C:29]([CH3:32])([CH3:31])[CH3:30])[CH:28]=1.CCN(C(C)C)C(C)C.C([O-])(O)=O.[Na+]>CN(C=O)C>[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9]([NH2:11])[N:8]([C:12]2[CH:17]=[C:16]([C:18](=[O:20])[NH:22][C:23]3[CH:28]=[C:27]([C:29]([CH3:31])([CH3:32])[CH3:30])[CH:26]=[C:25]([NH:33][S:34]([CH3:37])(=[O:36])=[O:35])[C:24]=3[O:38][CH3:39])[CH:15]=[CH:14][C:13]=2[CH3:21])[N:7]=1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 10214710N-(3-amino-5-tert-butyl-2-methoxy-phenyl)-methanesulfonamideHCID 57559704HCID 57559704, compound

Product 1

HCID 116995445-amino-1-[5-(5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenylcarbamoyl)-2-methyl-phenyl]-1H-pyrazole-3-carboxylic acid ethyl esterYield 48%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-Amino-1-(5-carboxy-2-methyl-phenyl)-1H-pyrazole-3-carboxylic acid ethyl ester (46 mg, 0.159 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′N′-tetramethyluronium hexafluorophosphate (HATU) (67 mg, 0.175 mmol) were combined in DMF (500 μL) and stirred for 5 min at room temperature N-(3-amino-5-tert-butyl-2-methoxy-phenyl)-methanesulfonamide (48 mg, 0.175 mmol) was added to the reaction mixture followed by i-Pr2NEt (83 μL, 0.477 mmol). The solution was stirred at room temperature for 48 h then poured onto saturated NaHCO3. The aqueous layer was extracted with CH2Cl2 and the combined extracts were dried over Na2SO4, filtered, and concentrated. Purification by semi-prep HPLC provided the title compound (41 mg, 48%) as a yellow solid (TFA salt): mp 104-111° C. (dec.); ESI MS m/z 544 [C26H33N5O6S+H]+; HPLC>98%, tR=20.79 min.

Workup

  1. additionwas added to the reaction mixture
  2. extractionThe aqueous layer was extracted with CH2Cl2
  3. dry with materialthe combined extracts were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by semi-prep HPLC

Sources & evidence

ORD record
ord-a3d5b5a791224f7b93395262553693ad
Source dataset
uspto-grants-2009_02
Patent number
US07485657B2

Reaction notes

Loading…