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Ammonium Chloride → 3-{3'-[(3-Methanesulfonyl-5-trifluoromethyl-benzoyl)-methyl-amino]-[3,4']bipyridinyl-2-yloxy}-azetidine-1-carboxylic acid tert-butyl ester

HRID 878376
Notes
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Reaction equation

HRID 878376 reaction equation
[CH3:1][NH:2][C:3]1[CH:4]=[N:5][CH:6]=[CH:7][C:8]=1[C:9]1[C:10]([O:15][CH:16]2[CH2:19][N:18]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:17]2)=[N:11][CH:12]=[CH:13][CH:14]=1.FC1C=CC=C(OC)C=1C1C=CN=CC=1N(CC(F)(F)F)[C:43](=[O:58])[C:44]1[CH:49]=[C:48]([C:50]([F:53])([F:52])[F:51])[CH:47]=[C:46]([S:54]([CH3:57])(=[O:56])=[O:55])[CH:45]=1.CCN(C(C)C)C(C)C.CS(C1C=C(C=C(C(F)(F)F)C=1)C(Cl)=O)(=O)=O.[NH4+].[Cl-]>C(Cl)Cl>[C:23]([O:22][C:20]([N:18]1[CH2:19][CH:16]([O:15][C:10]2[C:9]([C:8]3[CH:7]=[CH:6][N:5]=[CH:4][C:3]=3[N:2]([C:43](=[O:58])[C:44]3[CH:49]=[C:48]([C:50]([F:53])([F:51])[F:52])[CH:47]=[C:46]([S:54]([CH3:57])(=[O:56])=[O:55])[CH:45]=3)[CH3:1])=[CH:14][CH:13]=[CH:12][N:11]=2)[CH2:17]1)=[O:21])([CH3:26])([CH3:25])[CH3:24]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 5

HCID 25517Ammonium ChlorideHCID 81531Diisopropylethylamine2×HCID 70663657Tert-butyl 3-(3'-(methylamino)-3,4'-bipyridin-2-yloxy)azetidine-1-carboxylateHCID 86670807N-[4-(2-Fluoro-6-methoxy-phenyl)-pyridin-3-yl]-3-methanesulfonyl-N-(2,2,2-trifluoro-ethyl)-5-trifluoromethyl-benzamide2×HCID 866708083-(Methylsulfonyl)-5-(trifluoromethyl)benzoyl chloride

Product 1

HCID 706632583-{3'-[(3-Methanesulfonyl-5-trifluoromethyl-benzoyl)-methyl-amino]-[3,4']bipyridinyl-2-yloxy}-azetidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of tert-butyl 3-(3′-(methylamino)-3,4′-bipyridin-2-yloxy)azetidine-1-carboxylate (0.149 g, 418 μmol) in CH2Cl2 (4 mL) were added 3-(methylsulfonyl)-5-(trifluoromethyl)benzoyl chloride (240 mg, 836 μmol, example 223, intermediate d) and DIPEA (216 mg, 292 μL, 1.67 mmol) and the light yellow solution was stirred at room temperature for 24 hours. Another batch of 3-(methylsulfonyl)-5-(trifluoromethyl)benzoyl chloride (164 mg, 573 μmol) and DIPEA (162 mg, 219 μL, 1.25 mmol) was added and stirring was continued at room temperature for 24 hours. The reaction mixture was poured on saturated aqueous NH4Cl solution and CH2Cl2 and the layers were separated. The aqueous layer was extracted three times with CH2Cl2. The organic layers were dried over MgSO4, filtered, treated with silica gel and evaporated. The compound was twice purified by silica gel chromatography on a 20 g column using an MPLC system eluting with EtOAc. Light yellow gum (0.105 g; 41%). MS (ESI): m/z=607.18 [M+H]+.

Workup

  1. stirringstirring
  2. waitwas continued at room temperature for 24 hours
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted three times with CH2Cl2
  5. dry with materialThe organic layers were dried over MgSO4
  6. filtrationfiltered
  7. additiontreated with silica gel
  8. customevaporated
  9. customThe compound was twice purified by silica gel chromatography on a 20 g column
  10. washeluting with EtOAc

Sources & evidence

ORD record
ord-45d2884157ec4d30b20a229fd194aaee
Source dataset
uspto-grants-2015_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08987307B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes