Acetic Acid → Methyl (4-{4-[(4-chlorophenyl)(hydroxy)methyl]-3-cyano-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-2-thienyl}pyridin-2-yl)carbamate

HRID 2402089노트

반응식

HRID 2402089 반응식
[C:1]([C:3]1[C:7]([CH:8]=[O:9])=[C:6]([C:10]2[N:14]=[CH:13][N:12]([CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][O:16]3)[N:11]=2)[S:5][C:4]=1[C:21]1[CH:26]=[CH:25][N:24]=[C:23]([NH:27][C:28](=[O:31])[O:29][CH3:30])[CH:22]=1)#[N:2].[Cl:32][C:33]1[CH:38]=[CH:37][C:36]([Mg]Br)=[CH:35][CH:34]=1.CCOCC.C(O)(=O)C>O1CCCC1.CO.C(Cl)Cl>[Cl:32][C:33]1[CH:38]=[CH:37][C:36]([CH:8]([OH:9])[C:7]2[C:3]([C:1]#[N:2])=[C:4]([C:21]3[CH:26]=[CH:25][N:24]=[C:23]([NH:27][C:28](=[O:31])[O:29][CH3:30])[CH:22]=3)[S:5][C:6]=2[C:10]2[N:14]=[CH:13][N:12]([CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][O:16]3)[N:11]=2)=[CH:35][CH:34]=1

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 3283Diethyl EtherHCID 86667481Methyl (4-{3-cyano-4-formyl-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-2-thienyl}pyridin-2-yl)carbamateHCID 178478191HCID 178478191, 화합물

생성물 1

HCID 68100372Methyl (4-{4-[(4-chlorophenyl)(hydroxy)methyl]-3-cyano-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-2-thienyl}pyridin-2-yl)carbamate수율 82%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 21226129Dichloromethane methanol용매

실험 절차

To a suspension of methyl (4-{3-cyano-4-formyl-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-2-thienyl}pyridin-2-yl)carbamate (0.1077 g, 0.2456 mmol) in anhydrous Tetrahydrofuran (6.0 mL) cooled with ice bath was added slowly 1.0 M of 4-chlorophenylmagnesium bromide in ether (2.50 mL, 2.50 mmol). The resulting clear solution was stirred with cooling for 30 min, then the mixture was quenched with methanol (0.5 mL), then with acetic acid (148 mg, 2.46 mmol). The mixture was warmed to room temperature, then rotavaped to give crude product, which was chromatograph in a silica gel column using MeOH/DCM (0/100 to 3/97) to afford a solid product (0.116 g, yield 82%). LC/MS: (FA) ES+ 551; ES− 549. 1H NMR (400 MHz, d-chloroform/d4-methanol) δ 8.36 (s, 1H), 8.29 (m, 2H), 7.43 (m, 1H), 7.34 (m, 2H), 7.19 (m, 2H), 6.37 (s, 1H), 5.41-5.46 (m, 1H), 3.99-4.04 (m, 1H), 3.79 (s, 3H), 3.68-3.72 (m, 1H), 2.13 (m, 1H), 1.97-2.00 (m, 2H), 1.55-1.70 (m, br, 3H).

후처리

  1. temperaturecooled with ice bath
  2. temperaturewith cooling for 30 min
  3. customthe mixture was quenched with methanol (0.5 mL)
  4. customto give crude product, which

출처 및 근거

ORD 기록
ord-1a929b6b39bc48529be59970a338a27c
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08796271B2

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