Water → HCID 69417076, compound

HRID 1373203Notes

Reaction equation

HRID 1373203 reaction equation
FC1C(O[C:9]([C:11]2([F:30])[C:20]([NH:21][C:22]3[CH:27]=[CH:26][C:25]([I:28])=[CH:24][C:23]=3[CH3:29])=[CH:19][C:14]3=[N:15][CH2:16][N:17]([CH3:18])[C:13]3=[CH:12]2)=[O:10])=C(F)C(F)=C(F)C=1F.Cl.[NH2:36][NH2:37].C(N(CC)CC)C.O>ClCCl>[F:30][C:11]1([C:9]([NH:36][NH2:37])=[O:10])[C:20]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([I:28])=[CH:24][C:23]=2[CH3:29])=[CH:19][C:14]2=[N:15][CH2:16][N:17]([CH3:18])[C:13]2=[CH:12]1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 115031Hydrazinium chlorideHCID 86596374HCID 86596374, compound

Product 1

HCID 69417076HCID 69417076, compoundYield 42.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirring suspension of 5-fluoro-6-(4-iodo-2-methyl-phenylamino)-3-methyl-3H-benzoimidazole-5-carboxylic acid pentafluorophenyl ester (0.223 g, 0.355 mmol) and hydrazine hydrochloride (0.026 g, 0.355 mmol) in dichloromethane (10 mL) was added triethylamine (0.11 mL, 0.554 mmol). After stirring for 16 hours at ambient temperature, water was added to the reaction mixture. The afforded solids were filtered off and washed several times with water. The solids were dried under house vacuum at 60° C., which afforded 5-fluoro-6-(4-iodo-2-methyl-phenylamino)-3-methyl-3H-benzoimidazole-5-carboxylic acid hydrazide as a white solid (0.050 g, 42.4%). mp=232–234° C.; APCI+440.1; 1H NMR (400 MHz, DMSO-D6) δppm 2.3 (s, 3 H) 3.9 (s, 3 H) 6.2 (m, 1 H) 5.3 (m, 1 H) 5.3 (s, 2 H) 5.4 (s, 1 H) 5.5 (s, 1 H) 5.9 (s, 1 H) 8.3 (s,1 H). Step B: To a stirring solution of 5-fluoro-6-(4-iodo-2-methyl-phenylamino)-3-methyl-3H-benzoimidazole-5-carboxylic acid hydrazide (0.055 g, 0.125 mmol) in dioxane (5 mL) was added cyanogen bromide (0.015 g, 0.138 mmol) and NaHCO3 (0.12 g, 0.138 mmol) in water (1 mL) and the mixture was allowed to stir overnight at ambient temperature. To the reaction mixture was added saturated NaHCO3 and the afforded solids were filtered and washed with water. The solids were collected and dried in vacuo at 50° C. to afford [6-(5-amino-[1,3,4]oxadiazol-2-yl)-4-fluoro-1-methyl-1H-benzoimidazol-5-yl]-(4-iodo-2-methyl-phenyl)-amine (0.051 g, 88%). mp=258–260° C.; APCI+=465.0; 1H NMR (400 MHz, DMSO-D6) δ ppm 2.2 (s, 3 H) 3.8(s,3 H) 4.5 (s,2 H) 6.1 (m,1 H) 5.2 (d, J=9.0 Hz, 1 H) 5.4 (d, J=1.5 Hz, 1 H) 5.5(s, 1 H) 8.1 (s, 1 H) 8.3 (s, 1 H) 9.8 (s,1 H).

Workup

  1. filtrationThe afforded solids were filtered off
  2. washwashed several times with water
  3. customThe solids were dried under house vacuum at 60° C.

Sources & evidence

ORD record
ord-0e79168d6dae41d190d02a7d351fd2c1
Source dataset
uspto-grants-2007_01
Patent number
US07160915B2

Reaction notes

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