Diisopropylethylamine → 1-(t-butylamino)-N-(2-methyl-5-(3-(trifluoromethyl)benzamido)phenyl)isoquinoline-5-carboxamide

HRID 1051250Notes

Reaction equation

HRID 1051250 reaction equation
[C:1]([NH:5][C:6]1[C:15]2[CH:14]=[CH:13][CH:12]=[C:11]([C:16]([OH:18])=O)[C:10]=2[CH:9]=[CH:8][N:7]=1)([CH3:4])([CH3:3])[CH3:2].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.[NH2:52][C:53]1[CH:54]=[C:55]([NH:60][C:61](=[O:72])[C:62]2[CH:67]=[CH:66][CH:65]=[C:64]([C:68]([F:71])([F:70])[F:69])[CH:63]=2)[CH:56]=[CH:57][C:58]=1[CH3:59]>CN(C)C=O.C(OCC)(=O)C>[C:1]([NH:5][C:6]1[C:15]2[CH:14]=[CH:13][CH:12]=[C:11]([C:16]([NH:52][C:53]3[CH:54]=[C:55]([NH:60][C:61](=[O:72])[C:62]4[CH:67]=[CH:66][CH:65]=[C:64]([C:68]([F:69])([F:70])[F:71])[CH:63]=4)[CH:56]=[CH:57][C:58]=3[CH3:59])=[O:18])[C:10]=2[CH:9]=[CH:8][N:7]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

7

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 11529455N-(3-amino-4-methylphenyl)-3-(trifluoromethyl)benzamideHCID 825711051-(t-Butylamino)isoquinoline-5-carboxylic acid

Product 1

HCID 1180908921-(t-butylamino)-N-(2-methyl-5-(3-(trifluoromethyl)benzamido)phenyl)isoquinoline-5-carboxamideYield 18.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

1-(t-Butylamino)isoquinoline-5-carboxylic acid (0.33 g, 1.35 mmol) obtained in Step (6) of Preparation Example 1 was dissolved in dimethyl formamide (3 mL), added with HATU (0.62 g, 1.62 mmol) and DIPEA (0.47 mL, 2.70 mmol), and stirred for 10 minutes. The reaction mixture was added with N-(3-amino-4-methylphenyl)-3-(trifluoromethyl)benzamide (0.40 g, 1.35 mmol) obtained in Step (2) above, and stirred for 12 hours or more at room temperature. The reaction mixture was diluted with ethyl acetate, and washed with a saturated sodium bicarbonate solution and saline. The organic layer thus obtained was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrated compound was purified using silica gel chromatography to obtain the title compound (0.13 g, 18%).

Workup

  1. stirringstirred for 12 hours or more at room temperature
  2. washwashed with a saturated sodium bicarbonate solution and saline
  3. customThe organic layer thus obtained
  4. dry with materialwas dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe concentrated compound was purified

Sources & evidence

ORD record
ord-8e361e2ec76647039aaa5d59e86b7a8e
Source dataset
uspto-grants-2016_07
Patent number
US09388165B2

Reaction notes

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