Triethylamine → 6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3h-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amide

HRID 1895432Notes

Reaction equation

HRID 1895432 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]([C:19](O)=[O:20])=[CH:11][C:12]3[NH:16][CH:15]=[N:14][C:13]=3[C:17]=2[F:18])=[C:4]([Cl:22])[CH:3]=1.C1C=[CH:25][C:26]2N(O)N=N[C:27]=2[CH:28]=1.C(N(CC)CC)C.Cl.C1([N:44](C)[OH:45])CC1.CCN=C=NCCCN(C)C>CN(C=O)C.C(OCC)(=O)C.O>[CH:26]1([CH2:25][O:45][NH:44][C:19]([C:10]2[C:9]([NH:8][C:5]3[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][C:4]=3[Cl:22])=[C:17]([F:18])[C:13]3[N:14]=[CH:15][NH:16][C:12]=3[CH:11]=2)=[O:20])[CH2:27][CH2:28]1

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 211141586-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acidHCID 21114231Cyclopropyl methyl hydroxylamine hydrochloride

Product 1

HCID 98251576-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3h-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amideYield 89%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid 10b (22 mg, 0.057 mmol) is dissolved in DMF (1 mL) and HOBt (9 mg, 0.062 mmol) followed by triethyl amine (18 μL, 0.132 mmol) is added. Cyclopropyl methyl hydroxylamine hydrochloride (8 mg, 0.062 mmol) is added followed by EDCI (14 mg, 0.074 mmol). After 16 hours, the reaction mixture is diluted with ethyl acetate and water and the layers separated. The organic layer is washed with saturated NH4Cl, brine, saturated NaHCO3, water and brine. The organic layer is dried (MgSO4) and concentrated under reduced pressure to give 23 mg (89%) pure desired product. MS APCI (+) m/z 455, 453 (M+Br pattern) detected; MS APCI (−) m/z 453, 451 (M− Br pattern) detected; 1H NMR (400 MHz, DMSO-d6) δ 11.69 (broad s, 1H), 8.43 (s, 1H), 7.62 (d, 1H), 7.28 (dd, 1H), 6.42 (m, 1H), 3.63 (d, 2H), 1.03 (m, 1H), 0.48 (m, 2H), 0.19 (m, 2H); 19F NMR (376 MHz, DMSO-d6) −132.95 (s).

Workup

  1. additionis added
  2. customthe layers separated
  3. washThe organic layer is washed with saturated NH4Cl, brine, saturated NaHCO3, water and brine
  4. dry with materialThe organic layer is dried (MgSO4)
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-eaba420aad2043d695b4b719cd33f29f
Source dataset
uspto-grants-2013_08
Patent number
US08513293B2

Reaction notes

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