Water → HCID 178501268, compound

HRID 1035743Notes

Reaction equation

HRID 1035743 reaction equation
[CH3:1][O:2][C:3]([C@@H:5]1[CH2:10][CH2:9][C@H:8]([O:11][C:12]2[CH:20]=[CH:19][C:15]([C:16]([OH:18])=O)=[CH:14][CH:13]=2)[CH2:7][CH2:6]1)=[O:4].[F:21][C:22]1[CH:23]=[C:24]([CH:32]=[C:33]([F:35])[CH:34]=1)[CH2:25][C:26]1[S:30][C:29]([NH2:31])=[N:28][N:27]=1.C(N(C(C)C)CC)(C)C.O>CN(C)C=O>[F:35][C:33]1[CH:32]=[C:24]([CH:23]=[C:22]([F:21])[CH:34]=1)[CH2:25][C:26]1[S:30][C:29]([NH:31][C:16]([C:15]2[CH:14]=[CH:13][C:12]([O:11][C@@H:8]3[CH2:7][CH2:6][C@H:5]([C:3]([O:2][CH3:1])=[O:4])[CH2:10][CH2:9]3)=[CH:20][CH:19]=2)=[O:18])=[N:28][N:27]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 667401415-(3,5-Difluorobenzyl)-1,3,4-thiadiazol-2-amineHCID 178501272HCID 178501272, compound

Product 1

HCID 178501268HCID 178501268, compoundYield 38.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2.2 g of cis-4-(4-methoxycarbonylcyclohexyloxy)benzoic acid (7.91 mmol, 1 eq.) are placed in 30 mL of dimethylformamide at room temperature. 1.98 g of 5-(3,5-difluorobenzyl)[1.3.4]thiadiazol-2-ylamine (8.70 mmol, 1.1 eq.), 4.42 g of bromotris-pyrrolidinophosphonium hexafluorophosphonate (9.49 mmol, 1.2 eq.) and 2.76 mL of diisopropylethylamine (15.81 mmol, 2 eq.) are successively added. The reaction mixture is stirred for 6 days at room temperature, poured into water and extracted with ethyl acetate. The organic phase is washed three times with water and once with brine. The organic phase is concentrated and the residue is chromatographed on silica gel, eluting with a gradient of ethyl acetate in heptane ranging from 7% to 30%. 1.5 g of methyl cis-4-{4-[5-(3,5-difluorobenzyl)[1.3.4]thiadiazol-2-ylcarbamoyl]phenoxy}cyclohexanecarboxylate are obtained.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic phase is washed three times with water
  3. concentrationThe organic phase is concentrated
  4. customthe residue is chromatographed on silica gel
  5. washeluting with a gradient of ethyl acetate in heptane ranging from 7% to 30%

Sources & evidence

ORD record
ord-f4185056347f494695c4c9a037c8deb8
Source dataset
uspto-grants-2013_10
Patent number
US08546391B2

Reaction notes

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