Lithium Hydroxide → HCID 11740236, compound

HRID 2221486Notes

Reaction equation

HRID 2221486 reaction equation
[F:1][C:2]1[CH:21]=[CH:20][C:5]([CH2:6][N:7]2[C:11]3[CH:12]=[N:13][C:14]([C:16]([O:18]C)=O)=[CH:15][C:10]=3[N:9]=[CH:8]2)=[CH:4][CH:3]=1.F[C:23]1[CH:42]=[CH:41][C:26]([CH2:27]N2C3C=C(C(OC)=O)N=CC=3N=C2)=[CH:25][CH:24]=1.[NH:43]1C2C=C(C(OC)=O)N=CC=2N=C1.FC1C=CC(CBr)=CC=1.[Li+].[OH-:66]>CO>[CH2:27]([O:66][NH:43][C:16]([C:14]1[N:13]=[CH:12][C:11]2[N:7]([CH2:6][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:21][CH:20]=3)[CH:8]=[N:9][C:10]=2[CH:15]=1)=[O:18])[C:26]1[CH:41]=[CH:42][CH:23]=[CH:24][CH:25]=1

Participants

7

Reactant 5

HCID 3939Lithium HydroxideHCID 680214-Fluorobenzyl bromideHCID 21892226HCID 21892226, compoundHCID 21892245HCID 21892245, compound2×HCID 178497018HCID 178497018, compound

Product 1

HCID 11740236HCID 11740236, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Methyl 3-(4-fluorobenzyl)-3H-imidazo[4,5-c]pyridine-6-carboxylate and methyl 1-(4-fluorobenzyl)-1H-imidazo[4,5-c]pyridine-6-carboxylate. The title compounds were prepared by alkylation of methyl 1H-imidazo[4,5-c]pyridine-6-carboxylate with 4-fluorobenzyl bromide under the same conditions as those in step (a) of example 1. The two isomers were separated by column chromatography using ethyl acetate as eluent and characterized by NOESY 1H NMR. Methyl 3-(4-fluorobenzyl)-3H-imidazo[4,5-c]pyridine-6-carboxylate: 1H NMR (300 MHz, DMSO-d6) δ: 8.95 (s, 1H), 8.71 (s, 1H), 8.26 (s, 1H), 7.42-7.40 (m, 2H), 7.12-7.09 (m, 2H), 5.57 (s, 2H), 3.79 (s, 3H). LCMS (API-ES, M+H+): 286.1 Methyl 1-(4-fluorobenzyl)-1H-imidazo[4,5-c]pyridine-6-carboxylate: 1H NMR (300 MHz, DMSO-d6) δ: 8.96 (s, 1H), 8.67 (s, 1H), 8.31 (s, 1H), 7.35-7.33 (m, 2H), 7.14-7.08 (m, 2H), 5.57 (s, 2H), 3.79 (s, 3H). LCMS (API-ES, M+H+): 286.1. (b) 3-(4-Fluorobenzyl)-3H-imidazo[4,5-c]pyridine-6-carboxylic acid. Methyl 3-(4-fluorobenzyl)-3H-imidazo[4,5-c]pyridine-6-carboxylate (1.30 g, 4.56 mmol) in 30 ml 1 M LiOH in MeOH solution was stirred for 16 hours at ambient temperature. The mixture was concentrated to ⅓ of its volume in vacuo, and the pH of the concentrated solution was adjusted to 4-5 using 0.5 M hydrochloric acid. The precipitate that formed was collected by filtration and dried in vacuo to afford the title compound as a white powder (1.10 g, 88% yield). 1H NMR (300 MHz, MeOH-d4) δ: 8.73 (s, 1H), 8.56 (s, 1H), 8.39 (s, 1H), 7.36-7.34 (m, 2H), 7.07-7.02 (m, 2H), 5.57 (s, 2H). LCMS (API-ES, M+H+): 272.1. (c) N-Benzyloxy-3-(4-fluorobenzyl)-3H-imidazo[4,5-c]pyridine-6-carboxamide. The title compound was prepared by coupling of 3-(4-fluorobenzyl)-3H-imidazo[4,5-c]pyridine-6-carboxylic acid and N-benzyloxyamine hydrochloride under the same conditions as those in step (c) of example 1. 1H NMR (300 MHz, MeOH-d4) δ: 8.70 (s, 1H), 8.53 (s, 1H), 8.31 (s, 1H), 7.46-7.28 (m, 7H), 7.07-7.05 (m, 2H), 5.56 (s, 2H), 4.92 (s, 2H). LCMS (API-ES, M+H+): 377.1. HRMS calcd for C21H18FN4O2 (M+H) 377.1444, found 377.1424. HPLC: >91% purity.

Workup

  1. customThe two isomers were separated by column chromatography
  2. concentrationThe mixture was concentrated
  3. customThe precipitate that formed
  4. filtrationwas collected by filtration
  5. customdried in vacuo

Sources & evidence

ORD record
ord-42307c39db134a92be4f127144275790
Source dataset
uspto-grants-2008_05
Patent number
US07368571B2

Reaction notes

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