4-Methylmorpholine → methyl N-(2-fluoro-4-{5-[2-(methoxymethyl)-2'-methylbiphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzoyl)-N-methylglycinate

HRID 219963

반응식

HRID 219963 반응식
CN1CCOCC1.[F:8][C:9]1[CH:17]=[C:16]([C:18]2[N:22]=[C:21]([C:23]3[CH:28]=[CH:27][C:26]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=4[CH3:35])=[C:25]([CH2:36][O:37][CH3:38])[CH:24]=3)[O:20][N:19]=2)[CH:15]=[CH:14][C:10]=1[C:11](Cl)=[O:12].Cl.[CH3:40][O:41][C:42](=[O:46])[CH2:43][NH:44][CH3:45].[N-]=C=O>C1COCC1.CN(C=O)C>[F:8][C:9]1[CH:17]=[C:16]([C:18]2[N:22]=[C:21]([C:23]3[CH:28]=[CH:27][C:26]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=4[CH3:35])=[C:25]([CH2:36][O:37][CH3:38])[CH:24]=3)[O:20][N:19]=2)[CH:15]=[CH:14][C:10]=1[C:11]([N:44]([CH3:45])[CH2:43][C:42]([O:41][CH3:40])=[O:46])=[O:12]

참가 물질

7

반응물 4

HCID 79724-MethylmorpholineHCID 83544Glycine, N-methyl-, methyl ester, hydrochloride (1:1)HCID 105034IsocyanateHCID 866456572-Fluoro-4-{5-[2-(methoxymethyl)-2'-methylbiphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzoyl chloride

생성물 1

HCID 59495705methyl N-(2-fluoro-4-{5-[2-(methoxymethyl)-2'-methylbiphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzoyl)-N-methylglycinate

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of example 35 (2 170 mg; 5.2 mmol) in dry DCM (40 mL), oxalyl chloride (1 316 μl; 15.6 mmol) was added followed by dry DMF (40 μl). The reaction mixture was stirred at RT for 2 h and concentrated to afford 2-fluoro-4-{5-[2-(methoxymethyl)-2′-methylbiphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzoyl chloride as a white powder (2300 mg, 100%). In dry THF (1 mL) with a catalytic amount of DMF was swelled morpholinomethyl polystyrene high loading resin (NovaBiochem; 35.77 mg; 0.14 mmol), 3.9 mmol/g). 2-Fluoro-4-{5-[2-(methoxymethyl)-2′-methylbiphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzoyl chloride (25 mg; 0.06 mmol) was added followed by sarcosine methyl ester hydrochloride (15.98 mg; 0.11 mmol). The mixture was stirred overnight at rt. Isocyanate resin Si—NCO (Argonaut, 97 mg; 1.5 eq; 1.7 mmol/g) was added and the mixture stirred for 2 h. It was filtered through a SAX column (2 g) to obtain the title compound as a colorless oil. LC/MS (Method B): 504.2 (M+H)+ HPLC (Method A) Rt: 5.39 min (purity: 97%).

후처리

  1. stirringthe mixture stirred for 2 h
  2. filtrationIt was filtered through a SAX column (2 g)

출처 및 근거

ORD 기록
ord-d9bc41c69c0848029f5f7d1a5560fb41
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08202865B2

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