Lithium Hydroxide → HCID 11740236, 화합물

HRID 2221486노트

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HRID 2221486 반응식
[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

참가 물질

7

반응물 5

HCID 3939Lithium HydroxideHCID 680214-Fluorobenzyl bromideHCID 21892226HCID 21892226, 화합물HCID 21892245HCID 21892245, 화합물2회HCID 178497018HCID 178497018, 화합물

생성물 1

HCID 11740236HCID 11740236, 화합물수율 88%

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-42307c39db134a92be4f127144275790
출처 데이터셋
uspto-grants-2008_05
특허 번호
US07368571B2

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