Hydrochloric Acid → 3-[5-Amino-1-(5-cyclopropylcarbamoyl-2-methyl-phenyl)-1H-imidazole-4-carbonyl]-benzoic acid

HRID 251344Notes

Reaction equation

C([O:5][C:6](=[O:14])[C:7]1[CH:12]=[CH:11][CH:10]=[C:9](I)[CH:8]=1)(C)(C)C.C1([Mg]Cl)CCCCC1.[NH2:23][C:24]1[N:28]([C:29]2[CH:30]=[C:31]([CH:38]=[CH:39][C:40]=2[CH3:41])[C:32]([NH:34][CH:35]2[CH2:37][CH2:36]2)=[O:33])[CH:27]=[N:26][C:25]=1[C:42]#N.Cl.C([O-])([O-])=[O:46].[K+].[K+]>C1COCC1>[NH2:23][C:24]1[N:28]([C:29]2[CH:30]=[C:31]([C:32](=[O:33])[NH:34][CH:35]3[CH2:37][CH2:36]3)[CH:38]=[CH:39][C:40]=2[CH3:41])[CH:27]=[N:26][C:25]=1[C:42]([C:9]1[CH:8]=[C:7]([CH:12]=[CH:11][CH:10]=1)[C:6]([OH:5])=[O:14])=[O:46]

Participants

Conditions

Temperature: 42.5 °C

Procedure

To a solution of 3-iodobenzoic acid tert-butyl ester (4.6g) in THF (20 mL) at −40° C. under N2 was added cyclohexylmagnesium chloride (2M in THF, 8.5 mL). The solution was kept at −40° C. to 0° C. for 20 min., when 3-(5-amino-4-cyano-imidazol-1-yl)-N-cyclopropyl-4-methyl-benzamide was added and the reaction was kept at rt for 1 h. Then HCl (4 M, 10 mL) was added and the mixuture was heated at 40 to 45° C. overnight. The mixture was neutralized with K2CO3 solution and extracted with EtOAc (2×100 mL) and the combined organics dried over Na2SO4, and concentrated. Purification of the crude product by column chromatography (EtOAc: MeOH=6:1) gave the desired product (0.46 g).

Workup

waitthe reaction was kept at rt for 1 h
extractionextracted with EtOAc (2×100 mL)
dry with materialthe combined organics dried over Na2SO4
concentrationconcentrated
customPurification of the crude product by column chromatography (EtOAc: MeOH=6:1)

Sources & evidence

ORD record: ord-e8895aa343314f75a84b0cc7426139e9
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07863314B2

Reaction notes

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