Trifluoroacetic acid → N-[1-(4-fluoro-phenyl)-azetidin-3-ylmethyl]-4-(3-phenyl-indole-1-sulfonyl)-benzamide

HRID 1178971Notes

Reaction equation

HRID 1178971 reaction equation
FC(F)(F)C(O)=O.C(O[C:13](=[O:27])[NH:14][CH2:15][CH:16]1[CH2:19][N:18]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)[CH2:17]1)(C)(C)C.[C:28]1([C:34]2[C:42]3[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=3)[N:36]([S:43]([C:46]3[CH:54]=[CH:53][C:49](C(O)=O)=[CH:48][CH:47]=3)(=[O:45])=[O:44])[CH:35]=2)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.Cl.CN(C)CCCN=C=NCC>CN(C)C1C=CN=CC=1>[F:26][C:23]1[CH:22]=[CH:21][C:20]([N:18]2[CH2:17][CH:16]([CH2:15][NH:14][C:13](=[O:27])[C:49]3[CH:48]=[CH:47][C:46]([S:43]([N:36]4[C:37]5[C:42](=[CH:41][CH:40]=[CH:39][CH:38]=5)[C:34]([C:28]5[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=5)=[CH:35]4)(=[O:45])=[O:44])=[CH:54][CH:53]=3)[CH2:19]2)=[CH:25][CH:24]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 58975113[1-(4-Fluoro-phenyl)-azetidin-3-ylmethyl]-carbamic acid tert-butyl esterHCID 589751414-(3-Phenyl-indole-1-sulfonyl)-benzoic acid

Product 1

HCID 58975228N-[1-(4-fluoro-phenyl)-azetidin-3-ylmethyl]-4-(3-phenyl-indole-1-sulfonyl)-benzamideYield 12%

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Procedure

Add trifluoroacetic acid (2 mL) to [1-(4-fluoro-phenyl)-azetidin-3-ylmethyl]-carbamic acid tert-butyl ester (135 mg, 0.482 mmol) causing much gas evolution. Rotary evaporate the reaction solution (40° C.; azeotroping 3× with CH2Cl2). Dissolve this material in anhydr CH2Cl2 (3 mL). Add 4-(3-Phenyl-indole-1-sulfonyl)-benzoic acid (200 mg, 0.53 mmol, 1.1 equiv), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC; 140 mg, 0.73 mmol, 1.5 equiv), and 4-(dimethylamino)pyridine (DMAP; 270 mg, 2.3 mmol, 4.7 equiv). After stirring 16 h, transfer the reaction solution to a column of silica gel (80 mm×20 mm dia.) and elute (10-45% EtOAc/hex) to yield 31 mg (12%) of N-[1-(4-fluoro-phenyl)-azetidin-3-ylmethyl]-4-(3-phenyl-indole-1-sulfonyl)-benzamide as a light-yellow foam. MS (m/e): 539.99 (M+1); 538.16 (M−1).

Workup

  1. customRotary evaporate
  2. customthe reaction solution (40° C.; azeotroping 3× with CH2Cl2)
  3. dissolutionDissolve this material in anhydr CH2Cl2 (3 mL)
  4. washelute (10-45% EtOAc/hex)

Sources & evidence

ORD record
ord-2467be702f564ca58832f195c8f768c5
Source dataset
uspto-grants-2007_10
Patent number
US07276516B2

Reaction notes

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