Diisopropylethylamine → Methyl 4-[1-({[5-chloro-3-(3-chlorobenzyl)-2-thienyl]carbonyl}amino)ethyl]benzoate

HRID 870035Notes

Reaction equation

[Cl:1][C:2]1[S:6][C:5]([C:7]([OH:9])=O)=[C:4]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[CH:12]=2)[CH:3]=1.[Cl-].[CH3:19][O:20][C:21]([C:23]1[CH:28]=[CH:27][C:26]([CH:29]([NH3+:31])[CH3:30])=[CH:25][CH:24]=1)=[O:22].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C=O)C.O.CCOC(C)=O.CCOCC>[Cl:1][C:2]1[S:6][C:5]([C:7]([NH:31][CH:29]([C:26]2[CH:27]=[CH:28][C:23]([C:21]([O:20][CH3:19])=[O:22])=[CH:24][CH:25]=2)[CH3:30])=[O:9])=[C:4]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[CH:12]=2)[CH:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

The solution containing 5-chloro-3-(3-chlorobenzyl)thiophene-2-carboxylic acid from Example 1, Step 6 (200 mg, 0.696 mmol) and (±)-1-[4-(methoxycarbonyl)phenyl]ethanaminium chloride prepared according to Example 1, Steps 7 to 9 (180 mg, 0.835 mmol) in DMF was cooled to 0° C. and to it was added O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (317 mg, 0.835 mmol) followed by N,N-diisopropylethylamine (304 μL, 1.74 mmol, 2.5 eq) dropwise. The mixture was stirred at 0° C. for 15 min and diluted with water and EtOAc/ether. The organic layer was washed with water, brine, dried and filtered. The crude was purified by Combi Flash chromatography system (10-40% EtOAc/hexane in 15 min.) to give the desired product as a white solid.

Workup

customprepared
washThe organic layer was washed with water, brine
customdried
filtrationfiltered
customThe crude was purified by Combi Flash chromatography system (10-40% EtOAc/hexane in 15 min.)

Sources & evidence

ORD record: ord-e15bf5dd3f084f838ad4209abc02d0a9
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08969394B2

Reaction notes

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