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 2401828Notes

Reaction equation

HRID 2401828 reaction equation
[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

Participants

7

Reactant 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, compound

Product 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)carbamateYield 82%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-468a08cef2004413b253e26d9ea372b2
Source dataset
uspto-grants-2014_08
Patent number
US08796268B2

Reaction notes

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