m-Chloroperbenzoic acid → US9656988, Example 60

HRID 1050507Notes

Reaction equation

HRID 1050507 reaction equation
CS[C:3]1[N:4]=[N:5][C:6]([C:24]([NH2:26])=[O:25])=[C:7]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[O:17])=[CH:12][CH:11]=2)[N:8]=1.C1C=C(Cl)C=C(C(OO)=O)C=1.CCN(C(C)C)C(C)C.[NH2:47][C@@H:48]1[CH2:53][CH2:52][CH2:51][N:50]([C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[CH2:49]1>CN1C(=O)CCC1.CCOC(C)=O>[C:24]([C:6]1[N:5]=[N:4][C:3]([NH:47][C@@H:48]2[CH2:53][CH2:52][CH2:51][N:50]([C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[CH2:49]2)=[N:8][C:7]=1[NH:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)=[O:17])=[CH:12][CH:11]=1)(=[O:25])[NH2:26]

Participants

7

Reactant 4

HCID 70297m-Chloroperbenzoic acidHCID 81531DiisopropylethylamineHCID 1501974tert-butyl (3R)-3-aminopiperidine-1-carboxylateHCID 1181146503-(Methylthio)-5-(4-(morpholine-4-carbonyl)phenylamino)-1,2,4-triazine-6-carboxamide

Product 1

HCID 118114983US9656988, Example 60Yield 87%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of 3-(methylthio)-5-(4-(morpholine-4-carbonyl)phenylamino)-1,2,4-triazine-6-carboxamide (170 mg, 0.46 mmol) in NMP (20 mL) was added mCPBA (77% strength, 310 mg, 1.38 mmol). The mixture was stirred at RT for 1 h to yield a mixture of corresponding sulfone and sulfoxide. To the mixture was then added DIEA (0.40 mL, 2.30 mmol) and (R)-tert-butyl 3-aminopiperidine-1-carboxylate (184 mg, 0.92 mmol). The mixture was heated at 90° C. for 90 m. The mixture was cooled, diluted with 300 mL EtOAc, washed with 1N NaOH and brine, dried, and concentrated in vacuo. The residue was subjected to flash column chromatography with 0 to 6% MeOH in DCM to yield the title compound (74) (210 mg, 87% yield). MS found C25H34N8O5 as (M+H)+ 527.2, (M−H)− 525.3. UV: λ=252, 267, 283 nm.

Workup

  1. customto yield
  2. temperatureThe mixture was heated at 90° C. for 90 m
  3. temperatureThe mixture was cooled
  4. washwashed with 1N NaOH and brine
  5. customdried
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f555a36e764b4294bae3c143a85066fa
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

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