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 2401828ノート

反応式

HRID 2401828 の反応式
[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

参加物

7

反応物 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、化合物

生成物 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)carbamate収率 82%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 21226129Dichloromethane methanol溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-468a08cef2004413b253e26d9ea372b2
出典データセット
uspto-grants-2014_08
特許番号
US08796268B2

反応ノート

読み込み中…