Sodium Carbonate → HCID 178499303, compound

HRID 749386Notes

Reaction equation

HRID 749386 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][CH:3]=1.[CH3:11][O:12][C:13]([C:15]1[S:16][C:17](I)=[CH:18][C:19]=1[N:20]([C:28]([C@H:30]1[CH2:35][CH2:34][C@H:33]([CH3:36])[CH2:32][CH2:31]1)=[O:29])[CH:21]1[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]1)=[O:14].C1(C)C=CC=CC=1.CO.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1>[CH3:11][O:12][C:13]([C:15]1[S:16][C:17]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)=[CH:18][C:19]=1[N:20]([C:28]([C@H:30]1[CH2:31][CH2:32][C@H:33]([CH3:36])[CH2:34][CH2:35]1)=[O:29])[CH:21]1[CH2:22][CH2:23][N:24]([CH3:27])[CH2:25][CH2:26]1)=[O:14]

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 742994-Chlorophenylboronic acidHCID 21867641Toluene methanolHCID 178499357HCID 178499357, compound

Product 1

HCID 178499303HCID 178499303, compoundYield 72.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

To the mixture of 4-chlorophenylboronic acid (46.9 mg, 0.3 mmol) and 5-iodo-3-[(trans-4-methyl-cyclohexanecarbonyl)-(1-methyl-piperidin-4-yl)-amino]-thiophene-2-carboxylic acid methyl ester (50 mg, 0.099 mmol), from step 5, in 5:1 mixture of toluene/MeOH (2.0 mL) was added a solution of Pd(PPh3) 4 (12.0 mg, 0.01 mmol, 10 mol %) in toluene (1.0 mL) followed by aqueous 2M Na2CO3 solution (0.1 mL, 0.2 mmol). The resultant reaction mixture was heated at 70° C. for 16 h, cooled to room temperature, filtered off through MgSO4 and washed with EtOAc. Evaporation of the solvent and purification of the residue over preparative TLC (1 mm, 60A°) using DCM/CHCl3/MeOH/Et3N (100:90:16:1) as an eluent furnished 5-(4-chloro-phenyl)-3-[(trans-4-methyl-cyclohexanecarbonyl)-(1-methyl-piperidin-4-yl)-amino-]-thiopene-2-carboxylic acid methyl ester (35.0 mg, 71.5% yield). NMR 1H (CDCl3, 400 MHz): 7.53 (d, J=8.3, 2H), 7.4 (d, J=8.5, 2H), 7.0 (s, 1H), 4.67-4.58 (m, 1H), 3.84 (s, 3H), 2.82-2.64 (m, 1H), 2.2 (s, 3H), 2.14-1.35 (m), 0.763 (d, J=6.6, 3H), 0.76-0.56 (m, 2H).

Workup

  1. customThe resultant reaction mixture
  2. temperaturecooled to room temperature
  3. filtrationfiltered off through MgSO4
  4. washwashed with EtOAc
  5. customEvaporation of the solvent and purification of the residue over preparative TLC (1 mm, 60A°)

Sources & evidence

ORD record
ord-cfe363e1196641c68eb7fc51a42a6096
Source dataset
uspto-grants-2008_07
Patent number
US07402608B2

Reaction notes

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