Triethylamine → HCID 24960498, compound

HRID 1430634Notes

Reaction equation

HRID 1430634 reaction equation
[CH3:1][C:2]([O:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([NH:14][CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=2)[CH:9]=1)([CH3:6])[C:3](O)=[O:4].C(N(CC)CC)C.C1C=CC2N(O)N=NC=2C=1.[NH2:44][C:45]1[S:46][C:47]([Cl:50])=[CH:48][N:49]=1.CCN=C=NCCCN(C)C>C(Cl)Cl>[Cl:50][C:47]1[S:46][C:45]([NH:44][C:3](=[O:4])[C:2]([CH3:6])([O:7][C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([NH:14][CH2:15][CH2:16][C:17]3[CH:22]=[CH:21][C:20]([C:23]([F:25])([F:24])[F:26])=[CH:19][CH:18]=3)[CH:9]=2)[CH3:1])=[N:49][CH:48]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 389422-Amino-5-chlorothiazoleHCID 757711-HydroxybenzotriazoleHCID 59363821HCID 59363821, compound

Product 1

HCID 24960498HCID 24960498, compoundYield 30.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-Methyl-2-{3-[2-(4-trifluoromethyl-phenyl)-ethylamino]-phenoxy}-propionic acid (0.075 g, 0.204 mmol) in DCM (5 ml) added triethyl amine (0.034 ml, 0.24 mmol) and HOBt (0.0.037 g, 0.24 mmol) at 0° C. After stirring at this temperature for 5 min. added 2-amino-5-chlorothiazole (0.041 g, 0.285 mmol) and followed by EDCI (0.047 g, 0.244 mmol). The resulting solution was stirred for 12 h. then quenched with sat NH4Cl solution (15 ml). The aqueous phase was extracted with CH2Cl2 (3×50 ml). The organic phase were successively washed with 2% HCl (50 ml), brine (50 ml) and dried over Na2SO4. After evaporation, the residue was purified by flash chromatography (1:5 ethyl acetate:hexanes) to give N-(5-Chloro-thiazol-2-yl)-2-methyl-2-{3-[2-(4-trifluoromethyl-phenyl)-ethylamino]-phenoxy}-propionamide (0.03 g, 30%). 1H NMR (400 MHz, CDCl3): δ 1.59 (s, 6H), 2.96 (t, J=6.8 Hz, 2H), 3.39 (bs, 2H), 3.7 (bs, 1H), 6.18 (s, 1H), 6.26-6.38 (m, 2H), 7.07 (m, 1H), 7.31 (m, 2H), 7.58 (d, J=8 Hz, 2H), 10.0 (s, 1H), MS (EI) m/z: 484.1 (M+1).

Workup

  1. stirringThe resulting solution was stirred for 12 h.
  2. customthen quenched with sat NH4Cl solution (15 ml)
  3. extractionThe aqueous phase was extracted with CH2Cl2 (3×50 ml)
  4. washThe organic phase were successively washed with 2% HCl (50 ml), brine (50 ml)
  5. dry with materialdried over Na2SO4
  6. customAfter evaporation
  7. customthe residue was purified by flash chromatography (1:5 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-024febc249634db8a1f14ab58667a7f4
Source dataset
uspto-grants-2015_01
Patent number
US08940900B2

Reaction notes

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