Sodium Iodide → HCID 131736375, compound

HRID 1055481Notes

Reaction equation

HRID 1055481 reaction equation
[CH3:1][N:2]([C@@H:10]([CH3:31])[C:11](=[O:30])[NH:12][CH:13]1[C:19]2([CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)[O:18][C:17]2[CH:25]=[CH:26][CH:27]=[CH:28][C:16]=2[NH:15][C:14]1=[O:29])[C:3](=[O:9])[O:4][C:5]([CH3:8])([CH3:7])[CH3:6].Br[CH2:33][C:34]1[C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=2[O:36][N:35]=1.C([O-])([O-])=O.[Cs+].[Cs+].[Na+].[I-]>CN(C=O)C.CCOC(C)=O>[O:36]1[C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=2[C:34]([CH2:33][N:15]2[C:14](=[O:29])[C@@H:13]([NH:12][C:11](=[O:30])[C@@H:10]([N:2]([CH3:1])[C:3](=[O:9])[O:4][C:5]([CH3:8])([CH3:6])[CH3:7])[CH3:31])[C:19]3([CH2:20][CH2:21][O:22][CH2:23][CH2:24]3)[O:18][C:17]3[CH:25]=[CH:26][CH:27]=[CH:28][C:16]2=3)=[N:35]1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 34991891,2-Benzisoxazole, 3-(bromomethyl)-HCID 118574082HCID 118574082, compound

Product 1

HCID 131736375HCID 131736375, compoundYield 27%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of tert-butyl methyl((2S)-1-oxo-1-(4-oxo-2′,3′,4,5,5′,6′-hexahydro-3H-spiro[benzo[b][1,4]oxazepine-2,4′-pyran]-3-ylamino)propan-2-yl)carbamate (156 mg, 360 μmol), 3-(bromomethyl)benzo[d]isoxazole (83.9 mg, 396 μmol), Cs2CO3 (141 mg, 432 μmol) and NaI (64.7 mg, 432 μmol) in DMF (900 μL) was stirred at RT for 18 h, diluted with EtOAc, washed with H2O, brine, dried over Na2SO4, filtered, and the filtrate concentrated to give a residue that was purified by silica gel chromatography. The resulting material was purified by supercritical fluid chromatography (SFC) to provide tert-butyl (S)-1-((S)-5-(benzo[d]isoxazol-3-ylmethyl)-4-oxo-2′,3′,4,5,5′,6′-hexahydro-3H-spiro[benzo[b][1,4]oxazepine-2,4′-pyran]-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (54.5 mg, 27%) as a white foam.

Workup

  1. washwashed with H2O, brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationthe filtrate concentrated
  5. customto give a residue that
  6. customwas purified by silica gel chromatography
  7. customThe resulting material was purified by supercritical fluid chromatography (SFC)

Sources & evidence

ORD record
ord-4e5754faa0d645ff98b8dc97985c1645
Source dataset
uspto-grants-2016_07
Patent number
US09394263B2

Reaction notes

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