Pyrrolidine → HCID 71537485, compound

HRID 1519314Notes

Reaction equation

HRID 1519314 reaction equation
C[O:2][C:3]([C:5]1[C:6]([C:24]2[CH:29]=[CH:28][C:27]([C:30](O)=[O:31])=[CH:26][CH:25]=2)=[CH:7][CH:8]=[C:9]([C:11]2[S:12][CH:13]=[C:14]([C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([Cl:23])[CH:17]=3)[N:15]=2)[CH:10]=1)=[O:4].[NH:33]1[CH2:37][CH2:36][CH2:35][CH2:34]1>>[Cl:23][C:18]1[CH:17]=[C:16]([C:14]2[N:15]=[C:11]([C:9]3[CH:10]=[C:5]([C:3]([OH:2])=[O:4])[C:6]([C:24]4[CH:25]=[CH:26][C:27]([C:30]([N:33]5[CH2:37][CH2:36][CH2:35][CH2:34]5)=[O:31])=[CH:28][CH:29]=4)=[CH:7][CH:8]=3)[S:12][CH:13]=2)[CH:21]=[CH:20][C:19]=1[Cl:22]

Participants

3

Reactant 2

HCID 31268PyrrolidineHCID 86679835HCID 86679835, compound2×

Product 1

HCID 71537485HCID 71537485, compoundYield 54%

Procedure

Using the conditions of General Procedure E for Amide Coupling in Parallel Mode, 4-[4-(3,4-dichloro-phenyl)-thiazol-2-yl]-biphenyl-2,4′-dicarboxylic acid 2-methyl ester (which may be prepared as described for Intermediate 8; 100 mg, 0.21 mmol) was reacted with pyrrolidine (available from Aldrich Chemical Company, Inc.; 44 mg, 0.62 mmol). The resulting ester was hydrolyzed and the acid was purified using HPLC Purification Conditions B to give 4-[4-(3,4-dichloro-phenyl)-thiazol-2-yl]-4′-(pyrrolidine-1-carbonyl)-biphenyl-2-carboxylic acid (58 mg, 54%). 1H NMR (400 MHz, DMSO-d6) δ ppm 13.17 (br s, 1H), 8.46 (s, 1H), 8.35 (dd, J=11.7, 1.9 Hz, 2H), 8.23 (dd, J=8.2, 1.9 Hz, 1H), 8.09 (dd, J=8.5, 2.0 Hz, 1H), 7.76 (d, J=8.5 Hz, 1H), 7.59 (dd, J=8.3, 2.3 Hz, 3H), 7.46 (d, J=8.0 Hz, 2H), 3.40-3.54 (m, 4H), 1.73-2.01 (m, 4H).

Workup

  1. customthe acid was purified
  2. customHPLC Purification Conditions B

Sources & evidence

ORD record
ord-f1a32f9415c5495881536e65fa85bed6
Source dataset
uspto-grants-2015_07
Patent number
US09073881B2

Reaction notes

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