Water → HCID 86724315, compound

HRID 873765Notes

Reaction equation

HRID 873765 reaction equation
[F:1][C:2]1([F:34])[CH2:7][S:6][C:5]([NH:8]C(=O)C2C=CC=CC=2)=[N:4][C:3]21[C:25]1[C:20](=[CH:21][CH:22]=[C:23]([C:26]3[CH:27]=[N:28][CH:29]=[N:30][CH:31]=3)[CH:24]=1)[O:19][CH2:18][C:17]12[CH2:33][CH2:32]1.Cl.ONC.N1C=CC=CC=1.O>C(O)C.[Cl-].[Na+].O>[F:34][C:2]1([F:1])[CH2:7][S:6][C:5]([NH2:8])=[N:4][C:3]21[C:25]1[C:20](=[CH:21][CH:22]=[C:23]([C:26]3[CH:27]=[N:28][CH:29]=[N:30][CH:31]=3)[CH:24]=1)[O:19][CH2:18][C:17]12[CH2:32][CH2:33]1

Participants

7

Reactant 4

HCID 962WaterHCID 1049PyridineHCID 77906N-methylhydroxylamine hydrochlorideHCID 86724316HCID 86724316, compound

Product 1

HCID 86724315HCID 86724315, compoundYield 60.1%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of N-[5″,5″-difluoro-6′-(pyrimidin-5-yl)-5″,6″-dihydrodispiro[cyclopropane-1,3′-chromene-4′,4″-[1,3]thiazin]-2″-yl]benzamide (76 mg, 0.16 mmol) in ethanol (4 mL) were added N-hydroxymethanamine hydrochloride (133 mg, 1.59 mmol) and pyridine (126 mg, 1.59 mmol), and the mixture was stirred for 27 hours at 70° C. After cooling, H2O and brine were added and the mixture was extracted with chloroform. The organic layer was dried over MgSO4 and concentrated. The residue was purified by silica gel chromatography (EtOAc/hexane=50:50-100:0 and then EtOH/CHCl3=5:95) and a resultant solid was washed with iPr2O to give 5″,5″-difluoro-6′-(pyrimidin-5-yl)-5″,6″-dihydrodispiro[cyclopropane-1,3′-chromene-4′,4″-[1,3]thiazin]-2″-amine (36 mg).

Workup

  1. temperatureAfter cooling
  2. extractionthe mixture was extracted with chloroform
  3. dry with materialThe organic layer was dried over MgSO4
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel chromatography (EtOAc/hexane=50:50-100:0
  6. washEtOH/CHCl3=5:95) and a resultant solid was washed with iPr2O

Sources & evidence

ORD record
ord-28ba66a078ec4f82b01e1f73dadebd48
Source dataset
uspto-grants-2015_03
Patent number
US08975415B2

Reaction notes

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