Triethylamine → HCID 59828821, compound

HRID 1191092Notes

Reaction equation

HRID 1191092 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7]2[CH:21]=[CH:20][C:10]([CH2:11][NH:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[CH:9][CH:8]=2)[N:6]=1.C(N(CC)CC)C.[CH:29]1([C:32](Cl)=[O:33])[CH2:31][CH2:30]1>C(Cl)Cl.O1CCOCC1>[CH2:30]1[CH2:31][CH:29]1[C:32]([NH:1][C:2]1[S:3][CH:4]=[C:5]([C:7]2[CH:21]=[CH:20][C:10]([CH2:11][NH:12][C:13]([O:15][C:16]([CH3:18])([CH3:17])[CH3:19])=[O:14])=[CH:9][CH:8]=2)[N:6]=1)=[O:33]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 77637Cyclopropanecarbonyl chlorideHCID 58495559HCID 58495559, compound

Product 1

HCID 59828821HCID 59828821, compoundYield 65.3%

Reagents, catalysts & solvents 1

HCID 18626912Dioxane methylene chlorideSolvent

Procedure

To a mixture of 4-(2-aminothiazol-4-yl)-N-(tert-butoxycarbonyl)-benzylamine (2.98 g, 9.76 mmol) in DCM/dioxane (2:1, 150 mL) at room temperature, add triethylamine (2.0 mL, 15 mmol) and cyclopropanecarbonyl chloride (1.1 mL, 12 mmol). Stir at room temperature overnight and partition the reaction mixture between EtOAc (500 mL) and saturated aqueous NaHCO3 (250 mL). Dry the organic extract over Na2SO4, filter and concentrate in vacuo. Combine the residue with DCM and silica gel (12 g) and concentrate to a powder. Load powder on to a dry column attached to an Analogix® column (330 g) and purify by preparative liquid chromatography (0:1 to 1:4 EtOAc/hexane over 33 min, 1:4 EtOAc/hexane over 33 min, 1:4 to 1:1 EtOAc/hexane over 33 min, 1:1 EtOAc/hexane over 66 min; 35 mL/min) to afford the desired intermediate (2.381 g, 65%) as a yellow solid. MS (ES+) m/z: 374.2 (M+H)+.

Workup

  1. custompartition the reaction mixture between EtOAc (500 mL) and saturated aqueous NaHCO3 (250 mL)
  2. customDry the
  3. extractionorganic extract over Na2SO4
  4. filtrationfilter
  5. concentrationconcentrate in vacuo
  6. concentrationCombine the residue with DCM and silica gel (12 g) and concentrate to a powder
  7. custompurify by preparative liquid chromatography (0:1 to 1:4 EtOAc/hexane over 33 min, 1:4 EtOAc/hexane over 33 min, 1:4 to 1:1 EtOAc/hexane over 33 min, 1:1 EtOAc/hexane over 66 min; 35 mL/min)

Sources & evidence

ORD record
ord-8b05442e9c44407abd9e1953c054c525
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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