Diisopropylethylamine → tert-Butyl {4-[({4-[4-(3-chlorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}amino)carbonyl]benzyl}carbamate

HRID 82714

Reaction equation

HRID 82714 reaction equation
[NH2:1][C:2]1[C:3]([C:7]2[N:11]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[CH:13]=3)[C:10](=[O:19])[O:9][N:8]=2)=[N:4][O:5][N:6]=1.[C:20]([O:24][C:25]([NH:27][CH2:28][C:29]1[CH:37]=[CH:36][C:32]([C:33](O)=[O:34])=[CH:31][CH:30]=1)=[O:26])([CH3:23])([CH3:22])[CH3:21].C(N(CC)C(C)C)(C)C>ClCCl.CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[Cl:18][C:14]1[CH:13]=[C:12]([N:11]2[C:10](=[O:19])[O:9][N:8]=[C:7]2[C:3]2[C:2]([NH:1][C:33]([C:32]3[CH:31]=[CH:30][C:29]([CH2:28][NH:27][C:25](=[O:26])[O:24][C:20]([CH3:21])([CH3:22])[CH3:23])=[CH:37][CH:36]=3)=[O:34])=[N:6][O:5][N:4]=2)[CH:17]=[CH:16][CH:15]=1

Participants

7

Reactant 3

HCID 81531Diisopropylethylamine2×HCID 8536054-(((tert-Butoxycarbonyl)amino)methyl)benzoic acidHCID 585582673-(4-amino-1,2,5-oxadiazol-3-yl)-4-(3-chlorophenyl)-1,2,4-oxadiazol-5(4H)-one

Product 1

HCID 58558288tert-Butyl {4-[({4-[4-(3-chlorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}amino)carbonyl]benzyl}carbamate

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 3-(4-amino-1,2,5-oxadiazol-3-yl)-4-(3-chlorophenyl)-1,2,4-oxadiazol-5(4H)-one (0.5 g, 1.8 mmol) and 4-{[(tert-butoxycarbonyl)amino]methyl}benzoic acid (0.67 g, 2.7 mmol) in dichloromethane (35 mL) was treated with 4-dimethylaminopyridine (0.13 g, 1.1 mmol) and N,N-diisopropylethylamine (0.93 mL, 5.4 mmol) followed by bromotris(pyrrolydino)phosphonium hexafluorophosphate (1.3 g, 2.7 mmol) and additional N,N-diisopropylethylamine (0.93 mL, 5.4 mmol). The reaction mixture was stirred for 16 h, diluted with ethyl acetate (˜200 mL) and washed with 0.1 M HCl (2×100 mL) and brine (25 mL), dried with sodium sulfate, filtered, and concentrated. Purification of the crude reaction mixture on silica gel gave the intermediate tert-butyl {4-[({4-[4-(3-chlorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}amino)carbonyl]benzyl}carbamate. This material was diluted with dichloromethane (30 mL), treated with 4.0 M HCl in 1,4-dioxane (4.5 mL), and stirred for 1 h. The reaction mixture was concentrated and purified by preparative LCMS to give the desired product (542 mg, 58%). LCMS for C18H14ClN6O4 (M+H)+: m/z=413.0.

Workup

  1. washwashed with 0.1 M HCl (2×100 mL) and brine (25 mL)
  2. dry with materialdried with sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification of the crude
  6. customreaction mixture on silica gel

Sources & evidence

ORD record
ord-1e5af284cdd946f8a005667a589e68b2
Source dataset
uspto-grants-2014_09
Patent number
US08846726B2

Linked notes

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