Ammonium Chloride → HCID 70663302, compound

HRID 878306Notes

Reaction equation

HRID 878306 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[N:14]([CH3:28])[C:15](=[O:27])[C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([SH:26])[CH:17]=2)=[C:4]([O:29][CH3:30])[CH:3]=1.CCN(C(C)C)C(C)C.I[CH:41]1[CH2:44][N:43]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH2:42]1.[NH4+].[Cl-]>C(#N)C.CCOC(C)=O>[C:48]([O:47][C:45]([N:43]1[CH2:44][CH:41]([S:26][C:18]2[CH:19]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:21]=[C:16]([C:15](=[O:27])[N:14]([C:9]3[CH:10]=[N:11][CH:12]=[CH:13][C:8]=3[C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][C:4]=3[O:29][CH3:30])[CH3:28])[CH:17]=2)[CH2:42]1)=[O:46])([CH3:51])([CH3:49])[CH3:50]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 11000522Tert-butyl 3-iodoazetidine-1-carboxylateHCID 70663556HCID 70663556, compound

Product 1

HCID 70663302HCID 70663302, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of N-(4-(4-fluoro-2-methoxyphenyl)pyridin-3-yl)-3-mercapto-N-methyl-5-(trifluoromethyl)benzamide (0.35 g, 802 μmol, example 216, intermediate a) in acetonitrile (4 mL) was added DIPEA (259 mg, 350 μL, 2.00 mmol). The instantly formed yellow solution was treated with tert-butyl 3-iodoazetidine-1-carboxylate (284 mg, 1.0 mmol) and heated to reflux for 75 minutes. The reaction mixture was poured on saturated aqueous NH4Cl solution and EtOAc and the layers were separated. The aqueous layer was extracted twice with EtOAc. The organic layers were dried over MgSO4, filtered, treated with silica gel and evaporated. The compound was purified by silica gel chromatography on a 10 g column using an MPLC system eluting with a gradient of n-heptane:EtOAc (100:0 to 0:100). Colorless foam (0.405 g; 85%). MS (ESI): m/z=592.19 [M+H]+.

Workup

  1. temperatureheated
  2. temperatureto reflux for 75 minutes
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted twice with EtOAc
  5. dry with materialThe organic layers were dried over MgSO4
  6. filtrationfiltered
  7. additiontreated with silica gel
  8. customevaporated
  9. customThe compound was purified by silica gel chromatography on a 10 g column
  10. washeluting with a gradient of n-heptane:EtOAc (100:0 to 0:100)

Sources & evidence

ORD record
ord-e8d0023a11a8446ba29de8410939fa7e
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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