Diisopropylethylamine → 6-(4-Bromo-2-methyl-phenylamino)-7-fluoro-3-pent-4-enyl-3H-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amide

HRID 1895438Notes

Reaction equation

HRID 1895438 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]([C:24]([OH:26])=O)=[CH:11][C:12]3[N:16]([CH2:17][CH2:18][CH2:19][CH:20]=[CH2:21])[CH:15]=[N:14][C:13]=3[C:22]=2[F:23])=[C:4]([CH3:27])[CH:3]=1.CCN(C(C)C)C(C)C.C1CN([P+](ON2N=NC3C=[CH:58][CH:59]=[CH:60][C:55]2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.Cl.C1([N:74](C)[OH:75])CC1>C1COCC1.C(Cl)Cl.C(OCC)(=O)C>[CH:59]1([CH2:58][O:75][NH:74][C:24]([C:10]2[C:9]([NH:8][C:5]3[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][C:4]=3[CH3:27])=[C:22]([F:23])[C:13]3[N:14]=[CH:15][N:16]([CH2:17][CH2:18][CH2:19][CH:20]=[CH2:21])[C:12]=3[CH:11]=2)=[O:26])[CH2:60][CH2:55]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 211142136-(4-Bromo-2-methyl-phenylamino)-7-fluoro-3-pent-4-enyl-3H-benzoimidazole-5-carboxylic acidHCID 21114231Cyclopropyl methyl hydroxylamine hydrochloride

Product 1

HCID 588906146-(4-Bromo-2-methyl-phenylamino)-7-fluoro-3-pent-4-enyl-3H-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amideYield 70%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21919333Tetrahydrofurane dichloromethaneSolvent

Procedure

6-(4-Bromo-2-methyl-phenylamino)-7-fluoro-3-pent-4-enyl-3H-benzoimidazole-5-carboxylic acid 10d (0.390 g, 0.902 mmol) is dissolved in 1:1 THF/methylene chloride (6 mL) and Hunig's base (0.346 mL, 1.985 mmol) is added followed by PyBOP (0.563 g, 1.083 mmol). After 10 minutes, cyclopropyl methyl hydroxylamine hydrochloride (0.134 g, 1.083 mmol) is added. After 16 hours, the reaction mixture is diluted with ethyl acetate and washed with 0.1 N HCl, saturated NaHCO3, and brine. The organic layer is dried (Na2SO4) and concentrated under reduced pressure. The crude yellow residue is purified by FCC eluted with ethyl acetate to give 0.315 g (70%) pure desired product as a yellow solid: MS APCI (+) m/z 503, 501 (M+1 Br pattern) detected.

Workup

  1. additionis added
  2. waitAfter 16 hours
  3. washwashed with 0.1 N HCl, saturated NaHCO3, and brine
  4. dry with materialThe organic layer is dried (Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customThe crude yellow residue is purified by FCC
  7. washeluted with ethyl acetate

Sources & evidence

ORD record
ord-65e87bb68e2e4f3492e3b741ec1aa71d
Source dataset
uspto-grants-2013_08
Patent number
US08513293B2

Reaction notes

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