Dimethylformamide → HCID 178501267, compound

HRID 1035697Notes

Reaction equation

HRID 1035697 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].C(N(C(C)C)CC)(C)C.[CH2:30]([C:37]1[S:41][C:40]([NH2:42])=[N:39][N:38]=1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.CN(C=O)C>ClCCl>[CH2:30]([C:37]1[S:41][C:40]([NH:42][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:39][N:38]=1)[C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 81531Diisopropylethylamine2×HCID 7548235-Benzyl-1,3,4-thiadiazol-2-amine2×HCID 178501273HCID 178501273, compound

Product 1

HCID 178501267HCID 178501267, compoundYield 26.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

0.301 g of trans-4-(4-methoxycarbonylcyclohexyloxy)benzoic acid (1.08 mmol, 1 eq.) is placed in 5 mL of dichloromethane at room temperature. 0.36 mL of diisopropylethylamine (2.16 mmol, 2 eq.), 0.604 g of bromotris-pyrrolidinophosphonium hexafluorophosphonate (1.30 mmol, 1.2 eq.) and 0.207 g of 5-benzyl-1,3,4-thiadiazol-2-amine (1.08 mmol, 1 eq.) are successively added. 2 mL of DMF are then added. The reaction mixture is stirred for 18 hours at room temperature. 0.1 mL of diisopropylethylamine (0.6 mmol, 0.55 eq.), 0.2 g of bromotris-pyrrolidinophosphonium hexafluorophosphonate (0.43 mmol, 0.4 eq.) and 0.05 g of 5-benzyl-1,3,4-thiadiazol-2-amine (0.26 mmol, 0.24 eq.) are added. The reaction medium is stirred at 50° C. for 6 hours, diluted in dichloromethane, and washed with water and with saturated aqueous sodium bicarbonate solution. The organic phase is dried over magnesium sulfate and concentrated, and the residue is chromatographed on silica gel, eluting with a gradient of ethyl acetate in heptane ranging from 10% to 70%. The fractions of interest are evaporated. The solid obtained is triturated in ethanol to give 0.128 g of methyl trans-4-[4-(5-benzyl[1.3.4]thiadiazol-2-ylcarbamoyl)phenoxy]cyclohexanecarboxylate.

Workup

  1. stirringThe reaction medium is stirred at 50° C. for 6 hours
  2. washwashed with water and with saturated aqueous sodium bicarbonate solution
  3. dry with materialThe organic phase is dried over magnesium sulfate
  4. concentrationconcentrated
  5. customthe residue is chromatographed on silica gel
  6. washeluting with a gradient of ethyl acetate in heptane ranging from 10% to 70%
  7. customThe fractions of interest are evaporated
  8. customThe solid obtained
  9. customis triturated in ethanol

Sources & evidence

ORD record
ord-4d7f09d3b7834853a143ae5b076c94d9
Source dataset
uspto-grants-2013_10
Patent number
US08546391B2

Reaction notes

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