4-Aminotetrahydropyran → HCID 71538326, compound

HRID 1519319Notes

Reaction equation

HRID 1519319 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].[NH2:33][CH:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]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:29]=[CH:28][C:27]([C:30](=[O:31])[NH:33][CH:34]5[CH2:39][CH2:38][O:37][CH2:36][CH2:35]5)=[CH:26][CH:25]=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 4192234-AminotetrahydropyranHCID 86679835HCID 86679835, compound2×

Product 1

HCID 71538326HCID 71538326, compoundYield 28%

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 4-aminotetrahydropyran (available from Aldrich Chemical Company, Inc.; 63 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′-(tetrahydro-pyran-4-ylcarbamoyl)-biphenyl-2-carboxylic acid (32 mg, 28%). 1H NMR (400 MHz, DMSO-d6) δ ppm 13.08 (br s, 1H), 8.39 (s, 1H), 8.25-8.33 (m, 3H), 8.17 (dd, J=8.0, 1.8 Hz, 1H), 8.02 (dd, J=8.3, 2.0 Hz, 1H), 7.85 (d, J=8.3 Hz, 2H), 7.69 (d, J=8.5 Hz, 1H), 7.51 (d, J=8.0 Hz, 1H), 7.41 (d, J=8.3 Hz, 2H), 3.91-4.03 (m, 1H), 3.83 (d, J=9.8 Hz, 2H), 3.30-3.38 (m, 2H), 1.68-1.76 (m, 2H), 1.54 (qd, J=11.9, 4.3 Hz, 2H).

Workup

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

Sources & evidence

ORD record
ord-b98ec675751f492daa1268e500bad683
Source dataset
uspto-grants-2015_07
Patent number
US09073881B2

Reaction notes

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