Diisopropylethylamine → HCID 11296493, compound

HRID 730630Notes

Reaction equation

HRID 730630 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([S:8](=[O:11])(=[O:10])[NH2:9])[C:5]([O:12][CH3:13])=[CH:4][C:3]=1[CH2:14][C:15]([OH:17])=O.[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([CH:26]([NH2:40])[C:27]2[C:32]([N:33]3[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]3)=[CH:31][CH:30]=[CH:29][C:28]=2[CH3:39])=[CH:22][CH:21]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CCOC(C)=O.CN(C=O)C.C1COCC1>[Br:1][C:2]1[CH:7]=[C:6]([S:8](=[O:10])(=[O:11])[NH2:9])[C:5]([O:12][CH3:13])=[CH:4][C:3]=1[CH2:14][C:15]([NH:40][CH:26]([C:23]1[CH:22]=[CH:21][C:20]([O:19][CH3:18])=[CH:25][CH:24]=1)[C:27]1[C:32]([N:33]2[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]2)=[CH:31][CH:30]=[CH:29][C:28]=1[CH3:39])=[O:17]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57835214HCID 57835214, compoundHCID 57835218HCID 57835218, compound

Product 1

HCID 11296493HCID 11296493, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A reaction mixture containing (2-bromo-5-methoxy-4-sulfamoylphenyl)acetic acid 12f from Example 12 (18 mg, 0.06 mmol), 1-(4-methoxyphenyl)-1-(2-methyl-6-piperidin-1-ylphenyl)methylamine 8c from Example 8 (25.9 mg, 0.08 mmol), HATU (45.6 mg, 0.12 mmol) and DIPEA (0.06 ml, 0.3 mmol) in a solvent mixture of THF (1 mL) and DMF (0.3 mL) was stirred under argon at RT for 1 hour. The mixture was then diluted with EtOAc (7 mL) and the organic layer was washed with 1.0 M aqueous HCl (2 mL), saturated NaHCO3 (2 mL), dried over Na2SO4, concentrated to a minimum volume (˜1 mL) and purified by preparative TLC (eluent EtOAc:hexane:AcOH 60:40:1) to obtain 31 mg of the semi-pure final inhibitor (˜85% purity by 1H-NMR). The pure inhibitor 2-(2-bromo-5-methoxy-4-sulfamoylphenyl)-N-[1-(4-methoxyphenyl)-1-(2-methyl-6-piperidin-1-ylphenyl)methyl]acetamide 301 (Table 3) was isolated after further purification by C18 reversed phase HPLC.

Workup

  1. washthe organic layer was washed with 1.0 M aqueous HCl (2 mL), saturated NaHCO3 (2 mL)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated to a minimum volume (˜1 mL)
  4. custompurified by preparative TLC (eluent EtOAc:hexane:AcOH 60:40:1)
  5. customto obtain 31 mg of the semi-pure final inhibitor (˜85% purity by 1H-NMR)

Sources & evidence

ORD record
ord-8b515416baa54cf38b6663caee85095e
Source dataset
uspto-grants-2009_09
Patent number
US07582766B2

Reaction notes

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