1-Hydroxybenzotriazole → 3-({[2-amino-5-(trifluoromethyl)phenyl]carbamoyl}methyl)-N-methoxy-N-methylcyclobutane-1-carboxamide
Reaction equation
[CH3:1][O:2][N:3]([CH3:14])[C:4]([CH:6]1[CH2:9][CH:8]([CH2:10][C:11]([OH:13])=O)[CH2:7]1)=[O:5].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.[F:37][C:38]([F:48])([F:47])[C:39]1[CH:40]=[C:41]([NH2:46])[C:42]([NH2:45])=[CH:43][CH:44]=1>C(Cl)Cl>[NH2:45][C:42]1[CH:43]=[CH:44][C:39]([C:38]([F:37])([F:47])[F:48])=[CH:40][C:41]=1[NH:46][C:11]([CH2:10][CH:8]1[CH2:7][CH:6]([C:4]([N:3]([O:2][CH3:1])[CH3:14])=[O:5])[CH2:9]1)=[O:13]Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
TEA (1.49 ml, 10.70 mmol) was added to a suspension of 2-{3-[methoxy(methyl)carbamoyl]cyclobutyl}acetic acid, EDC.HCl 1.18 g, 6.20 mmol), HOBt.xH2O (0.77 g, 5.69 mmol) in DCM (20 ml) at 0° C. and stirred for 5 min before the addition of 4-(trifluoromethyl)benzene-1,2-diamine (1.04 g, 10.34 mmol). This was stirred for a further 20 min at 0° C. then allowed to warm to RT. The reaction was monitored by LC MS, after 2 hours the reaction mixture was washed with 1N HCl (50 ml) then sat. NaHCO3 (50 ml). This was dried over Na2SO4, filtered and evaporated to dryness. Purification by silica gel column chromatography, eluting with EtOAc gave the desired product (0.83 g, 44%) as a beige solid;
Workup
- temperatureto warm to RT
- waitThe reaction was monitored by LC MS, after 2 hours
- washthe reaction mixture was washed with 1N HCl (50 ml)
- dry with materialThis was dried over Na2SO4
- filtrationfiltered
- customevaporated to dryness
- customPurification by silica gel column chromatography
- washeluting with EtOAc
Sources & evidence
- ORD record
- ord-5e5112338c8d463185bbb553982433d8
- Source dataset
- uspto-grants-2013_11
- Patent number
- US08580762B2
Reaction notes
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