3-Chlorobenzoic Acid → 3-Chloro-N-{1-(1,4-dioxa-8-azaspiro[4.5]dec-8-ylcarbonyl)-5-[4-(trifluoromethyl)phenyl]piperidin-3-yl}benzenecarboxamide
Reaction equation
CCN(C(C)C)C(C)C.[Cl:10][C:11]1[CH:12]=[C:13]([CH:17]=[CH:18][CH:19]=1)[C:14]([OH:16])=O.Cl.[NH2:21][CH:22]1[CH2:27][CH:26]([C:28]2[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=2)[CH2:25][N:24]([C:38]([N:40]2[CH2:49][CH2:48][C:43]3([O:47][CH2:46][CH2:45][O:44]3)[CH2:42][CH2:41]2)=[O:39])[CH2:23]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Cl:10][C:11]1[CH:12]=[C:13]([C:14]([NH:21][CH:22]2[CH2:27][CH:26]([C:28]3[CH:33]=[CH:32][C:31]([C:34]([F:36])([F:37])[F:35])=[CH:30][CH:29]=3)[CH2:25][N:24]([C:38]([N:40]3[CH2:41][CH2:42][C:43]4([O:47][CH2:46][CH2:45][O:44]4)[CH2:48][CH2:49]3)=[O:39])[CH2:23]2)=[O:16])[CH:17]=[CH:18][CH:19]=1Participants
6
Reactant 4
HCID 4473-Chlorobenzoic Acid
HCID 81531Diisopropylethylamine
HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)
HCID 66760651{3-Amino-5-[4-(trifluoromethyl)phenyl]piperidin-1-yl}(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)methanone hydrochlorideProduct 1
Reagents, catalysts & solvents 1
Procedure
0.59 ml (3.38 mmol) of N,N′-diisopropylethylamine and 248 mg (1.58 mmol) of 3-chlorobenzoic acid were added to a solution of the compound from Example 62A (500 mg, 1.06 mmol) in N,N′-dimethylformamide (18 ml). After addition of 522 mg (1.37 mmol) of HATU, the mixture was stirred at RT overnight. The reaction mixture was purified directly by preparative HPLC(RP18 column; acetonitrile/water gradient). Yield: 414 mg (67% of theory)
Workup
- customThe reaction mixture was purified directly by preparative HPLC(RP18 column
Sources & evidence
- ORD record
- ord-cb14622e14d94ee59f538435f4589064
- Source dataset
- uspto-grants-2015_03
- Patent number
- US08987248B2
Reaction notes
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