Diisopropylethylamine → HCID 86682809, compound

HRID 1504333Notes

Reaction equation

HRID 1504333 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[C:4]([F:11])[C:3]=1[O:12][C:13]([F:16])([F:15])[F:14].[NH2:17][C:18]1[CH:19]=[CH:20][C:21]([N:24]2[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][C@H:25]2[CH3:37])=[N:22][CH:23]=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>CN(C=O)C>[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:17][C:18]2[CH:19]=[CH:20][C:21]([N:24]3[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][C@H:25]3[CH3:37])=[N:22][CH:23]=2)=[O:8])=[C:4]([F:11])[C:3]=1[O:12][C:13]([F:16])([F:15])[F:14]

Participants

6

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 67495583HCID 67495583, compoundHCID 76848194HCID 76848194, compound

Product 1

HCID 86682809HCID 86682809, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-bromo-2-fluoro-3-(trifluoromethoxy)benzoic acid (150 mg, 0.50 mmol, Preparation 52), (R)-tert-butyl 4-(5-aminopyridin-2-yl)-3-methylpiperazine-1-carboxylate (145 mg, 0.50 mmol), and HATU (235 mg, 0.62 mmol) dissolved in DMF (1 mL) was added DIPEA (0.43 mL, 2.48 mmol). The reaction mixture was stirred at RT for 1 h, extracted with EtOAc (80 mL) washed with water (3×20 mL) and brine (20 mL), dried over sodium sulfate, filtered, concentrated, and purified by silica gel chromatography (12 g silica gel, 0-40% EtOAc:hexanes over 20 min), to provide the title intermediate (203 mg, 71% yield) as a yellow solid. (m/z): [M+H]+ calcd for C23H25BrF4N4O4 577.10; 579.10. found 579.0.

Workup

  1. extractionextracted with EtOAc (80 mL)
  2. washwashed with water (3×20 mL) and brine (20 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by silica gel chromatography (12 g silica gel, 0-40% EtOAc:hexanes over 20 min)

Sources & evidence

ORD record
ord-86a28017ff154d9eb6e7ccd913677095
Source dataset
uspto-grants-2015_12
Patent number
US09212168B2

Reaction notes

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