1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 59458716, compound

HRID 1874283Notes

Reaction equation

HRID 1874283 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:8]([C@@:11]([NH:33][C:34](=O)[C:35]2[CH:40]=[CH:39][C:38]([F:41])=[C:37]([C:42]([F:45])([F:44])[F:43])[CH:36]=2)([C:19]2[CH:24]=[C:23]([O:25][C:26]([F:31])([F:30])[CH:27]([F:29])[F:28])[CH:22]=[C:21]([F:32])[CH:20]=2)[CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:7][C:3]=1[C:4](O)=[O:5].OC1C2N=NNC=2C=CC=1.CCN=C=NCCCN(C)C.[OH2:68].[NH2:69][NH2:70]>ClCCl>[F:41][C:38]1[CH:39]=[CH:40][C:35]([C:34]([NH:33][C@:11]([C:8]2[CH:9]=[CH:10][C:2]([F:1])=[C:3]([C:4]([NH:69][NH2:70])=[O:5])[CH:7]=2)([C:19]2[CH:24]=[C:23]([O:25][C:26]([F:31])([F:30])[CH:27]([F:28])[F:29])[CH:22]=[C:21]([F:32])[CH:20]=2)[CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:68])=[CH:36][C:37]=1[C:42]([F:45])([F:44])[F:43]

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 24654Hydrazine hydrate (1:1)HCID 59459122HCID 59459122, compoundHCID 178418300HCID 178418300, compound

Product 1

HCID 59458716HCID 59458716, compoundYield 81%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-2-fluoro-5-(1-(4-fluoro-3-(trifluoromethyl)benzamido)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)benzoic acid, prepared as described in Procedures 3, 62, 5, 6, 7, 56, 57 and 23, (30 mg, 0.045 mmol) in dichloromethane (1 mL) was added hydroxybenzotriazole (8 mg, 0.058 mmol), followed by EDCI (11 mg, 0.058 mmol). The reaction mixture was stirred for 15 min at rt, then hydrazine hydrate was added (3 μL, 0.001 mmol) and the reaction mixture was stirred for an additional 15 min. The reaction mixture was loaded on an ISCO cartridge (4 g column) and eluted with 0 to 100% EtOAc in hexane to yield (R)-4-fluoro-N-(1-(4-fluoro-3-(hydrazinecarbonyl)phenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-3-(trifluoromethyl)benzamide (Example 344, 25 mg, 81% yield) as a white solid. LCMS: RT=1.78 min [M+H] 674 (Chromolith Performance RP-18e column, 4.6×100 mm eluting with 10-90% ACN/H2O over 2 minutes containing 0.1% TFA, 5 mL/min, monitoring at 220 nm).

Workup

  1. stirringthe reaction mixture was stirred for an additional 15 min
  2. washeluted with 0 to 100% EtOAc in hexane

Sources & evidence

ORD record
ord-3d72d14c07724b3b8c9472dc2dd02c0e
Source dataset
uspto-grants-2012_11
Patent number
US08304403B2

Reaction notes

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