Diisopropylethylamine → HCID 90229446, compound

HRID 1505807Notes

Reaction equation

HRID 1505807 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][CH:13]2[CH2:15][CH2:14]2)=[CH:7][C:3]=1[C:4]([OH:6])=O.[NH2:16][C:17]1[CH:18]=[C:19]([C:29]([NH:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([Cl:38])[C:33]=2[CH3:39])=[O:30])[C:20]2[N:24]=[C:23]([N:25]([CH3:27])[CH3:26])[NH:22][C:21]=2[CH:28]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C=O)C.C(OCC)(=O)C>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][CH:13]2[CH2:15][CH2:14]2)=[CH:7][C:3]=1[C:4]([NH:16][C:17]1[CH:18]=[C:19]([C:29]([NH:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([Cl:38])[C:33]=2[CH3:39])=[O:30])[C:20]2[N:24]=[C:23]([N:25]([CH3:26])[CH3:27])[NH:22][C:21]=2[CH:28]=1)=[O:6]

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 90229258HCID 90229258, compoundHCID 90229424HCID 90229424, compound

Product 1

HCID 90229446HCID 90229446, compoundYield 93.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-chloro-5-(cyclopropylethynyl)benzoic acid (33 mg, Reference Example 3), 6-amino-N-(3-chloro-2-methylphenyl)-2-(dimethylamino)-1H-benzimidazole-4-carboxamide (50 mg) and HATU (72 mg) in DMF (1 mL), was added N,N-diisopropylethylamine (66 μL), and the mixture was stirred at room temperature for 17 hours. The reaction mixture was diluted with ethyl acetate, and washed sequentially with saturated aqueous sodium bicarbonate and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified on column chromatography to obtain 6-({[2-chloro-5-(cyclopropylethynyl)phenyl]carbonyl}amino)-N-(3-chloro-2-methylphenyl)-2-(dimethylamino)-1H-benzimidazole-4-carboxamide (74 mg). This was suspended in MeOH (1 mL), 2N hydrogen chloride/EtOH solution (1 Eq) was added to obtain a homogeneous solution, and the solvent was removed under reduced pressure. The residue was triturated in ethyl acetate, and the precipitate was collected by filtration and dried under reduced pressure to obtain the titled compound (58 mg) as pale yellow powder.

Workup

  1. washwashed sequentially with saturated aqueous sodium bicarbonate and brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified on column chromatography

Sources & evidence

ORD record
ord-21d9ba0cd840456394a4656080c4d5db
Source dataset
uspto-grants-2015_12
Patent number
US09216968B2

Reaction notes

Loading…