Diisopropylethylamine → Methyl 2-chloro-4-(5-{4-(2-methylpiperidin-1-yl)-3-[(methylsulfonyl)amino]phenyl}-1,2,4-oxadiazol-3-yl)benzoate

HRID 219944Notes

Reaction equation

HRID 219944 reaction equation
[CH3:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][N:3]1[C:8]1[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][C:9]=1[NH:17][S:18]([CH3:21])(=[O:20])=[O:19].[NH2:22][C:23](=[N:35]O)[C:24]1[CH:33]=[CH:32][C:27]([C:28]([O:30][CH3:31])=[O:29])=[C:26]([Cl:34])[CH:25]=1.Cl.C(N=C=NCCCN(C)C)C.CCN(C(C)C)C(C)C>CC#N.C1COCC1>[Cl:34][C:26]1[CH:25]=[C:24]([C:23]2[N:22]=[C:12]([C:11]3[CH:15]=[CH:16][C:8]([N:3]4[CH2:4][CH2:5][CH2:6][CH2:7][CH:2]4[CH3:1])=[C:9]([NH:17][S:18]([CH3:21])(=[O:20])=[O:19])[CH:10]=3)[O:14][N:35]=2)[CH:33]=[CH:32][C:27]=1[C:28]([O:30][CH3:31])=[O:29]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 584433444-(2-Methylpiperidin-1-yl)-3-[(methylsulfonyl)amino]benzoic acidHCID 72307499Methyl 4-[amino(hydroxyimino)methyl]-2-chlorobenzoate

Product 1

HCID 67529156Methyl 2-chloro-4-(5-{4-(2-methylpiperidin-1-yl)-3-[(methylsulfonyl)amino]phenyl}-1,2,4-oxadiazol-3-yl)benzoate

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

In a 2-5 microwave vial, placed in a dry-ice acetone bath, was added THF (2 mL) and CH3CN (2 mL) to a mixture of Intermediate 25 (156.19 mg; 0.50 mmol), Intermediate 34 (114.32 mg; 0.50 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (115.02 mg; 0.60 mmol). The reaction mixture was allowed to warm to RT for half a hour then DIEA (204.07 μL; 1.20 mmol) was added and the mixture was heated by microwave irradiation at 150° C. for 30 min. The reaction mixture was filtered through a SPE NH2 column (2 g) and rinsed with ACN. The filtrate was passed through a SPE SCX column (2 g) and rinsed with ACN. After evaporation of the solvents, the crude product was purified by flash chromatography (c-hex/EtOAc: 9.5/0.5), affording the title compound. LC/MS (Method B): 503.4 (M−H)−, 505.3 (M+H)+. HPLC (Method A) Rt 5.64 min (Purity: 100.0%).

Workup

  1. customIn a 2-5 microwave vial, placed in a dry-ice acetone bath
  2. temperaturethe mixture was heated by microwave irradiation at 150° C. for 30 min
  3. filtrationThe reaction mixture was filtered through a SPE NH2 column (2 g)
  4. washrinsed with ACN
  5. washrinsed with ACN
  6. customAfter evaporation of the solvents
  7. customthe crude product was purified by flash chromatography (c-hex/EtOAc: 9.5/0.5)

Sources & evidence

ORD record
ord-11a98934fbd641819b2e5047744c180a
Source dataset
uspto-grants-2012_06
Patent number
US08202865B2

Reaction notes

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