Diisopropylethylamine → HCID 67460072, compound

HRID 1804493Notes

Reaction equation

HRID 1804493 reaction equation
F[C:2]([C:4]1[O:8][N:7]=[C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:5]=1[C:15]([O:17][CH3:18])=[O:16])=[O:3].O/[N:20]=[C:21](/[C:23]1[CH:40]=[CH:39][C:26]([CH2:27][N:28]2[CH2:31][CH:30]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:29]2)=[CH:25][CH:24]=1)\[NH2:22].C(N(C(C)C)CC)(C)C>C(#N)C>[C:35]([O:34][C:32]([CH:30]1[CH2:31][N:28]([CH2:27][C:26]2[CH:39]=[CH:40][C:23]([C:21]3[N:22]=[C:2]([C:4]4[O:8][N:7]=[C:6]([C:9]5[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=5)[C:5]=4[C:15]([O:17][CH3:18])=[O:16])[O:3][N:20]=3)=[CH:24][CH:25]=2)[CH2:29]1)=[O:33])([CH3:38])([CH3:36])[CH3:37]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 58504340HCID 58504340, compoundHCID 58537232HCID 58537232, compound

Product 1

HCID 67460072HCID 67460072, compoundYield 62.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a mixture of methyl 5-(fluorocarbonyl)-3-phenylisoxazole-4-carboxylate (99 mg, 0.397 mmol) and (Z)-tert-butyl 1-(4-(N′-hydroxycarbamimidoyl)benzyl)azetidine-3-carboxylate (121 mg, 0.397 mmol) in acetonitrile (2 mL) at rt was added diisopropylethylamine (0.083 mL, 0.477 mmol) and the reaction mixture was allowed to stir at rt over the weekend. The reaction mixture was partitioned between EtOAc (30 mL) and water (30 mL). The organic layer was washed with brine (20 mL), dried (MgSO4) and concentrated to afford a white solid that was chromatographed on a 12 gm Isco silica gel cartridge, eluting with a 0-100% EtOAc/Hex gradient. The essentially pure fractions containing product were concentrated to afford methyl 5-(3-(4-((3-(tert-butoxycarbonyl)azetidin-1-yl)methyl)phenyl)-1,2,4-oxadiazol-5-yl)-3-phenylisoxazole-4-carboxylate (128 mg, 0.248 mmol, 62.4% yield) as a white solid. HPLC retention time=1.78 minutes (YMC Combi 4.6×30 mm S-5 ODS column) eluting with 10-90% aqueous methanol+0.1 TFA a 2 minute gradient. MS: (M+H)=517.22. 1H NMR (400 MHz, chloroform-d) d ppm 1.45 (s, 9H) 3.23-3.32 (m, 3H) 3.51-3.58 (m, 2H) 3.68 (s, 2H) 3.95 (s, 3H) 7.44 (d, J=8.0 Hz, 2H) 7.48-7.56 (m, 3H) 7.75 (dd, J=7.91, 1.63 Hz, 2H) 8.11 (d, J=8.3 Hz, 2H).

Workup

  1. customThe reaction mixture was partitioned between EtOAc (30 mL) and water (30 mL)
  2. washThe organic layer was washed with brine (20 mL)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customto afford a white solid
  6. customthat was chromatographed on a 12 gm Isco silica gel cartridge
  7. washeluting with a 0-100% EtOAc/Hex gradient
  8. additionThe essentially pure fractions containing product
  9. concentrationwere concentrated

Sources & evidence

ORD record
ord-0e388eec1d9d4d1d8911b05ec94bed8c
Source dataset
uspto-grants-2013_01
Patent number
US08354398B2

Reaction notes

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