Methyl iodide → HCID 117667526, compound

HRID 712734Notes

Reaction equation

HRID 712734 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][C:14]([C:18]3[CH:19]=[N:20][CH:21]=[C:22]([CH2:24][NH:25][C:26]([CH:28]4[CH2:33][CH2:32][O:31][CH2:30][CH2:29]4)=[O:27])[CH:23]=3)=[CH:15][N:16]=2)[CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].I[CH3:37].[NH4+].[Cl-]>CN(C=O)C.CCOC(C)=O.O>[C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][C:14]([C:18]3[CH:19]=[N:20][CH:21]=[C:22]([CH2:24][N:25]([CH3:37])[C:26]([CH:28]4[CH2:33][CH2:32][O:31][CH2:30][CH2:29]4)=[O:27])[CH:23]=3)=[CH:15][N:16]=2)[CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 117667823HCID 117667823, compound

Product 1

HCID 117667526HCID 117667526, compoundYield 51.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

6-(5-{[(Tetrahydro-pyran-4-carbonyl)-amino]-methyl}-pyridin-3-yl)-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid tert-butyl ester (132 mg, 0.29 mmol) is dissolved in DMF (4.0 mL) and cooled down to 0° C. Sodium hydride 60% in mineral oil (14 mg, 0.35 mmol) is added and the mixture is stirred for 10 min. Then iodomethane (0.036 mL, 0.58 mmol) is added and the reaction mixture is warmed up to room temperature for 2 hrs. Saturated NH4Cl aqueous solution (2.0 mL) is added along with water (10 mL) and EtOAc (15 mL). The mixture is stirred for 10 min, the aqueous layer is separated and extracted with EtOAc (2×10 mL). The organic layers are combined and concentrated to give the crude product. Purification by flash column chromatography affords 70 mg of 6-(5-{[methyl-(tetrahydro-pyran-4-carbonyl)-amino]-methyl}-pyridin-3-yl)-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid tert-butyl ester.

Workup

  1. temperaturethe reaction mixture is warmed up to room temperature for 2 hrs
  2. stirringThe mixture is stirred for 10 min
  3. customthe aqueous layer is separated
  4. extractionextracted with EtOAc (2×10 mL)
  5. concentrationconcentrated
  6. customto give the crude product
  7. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-e81a6e7de2074399b76f3c83998d7afb
Source dataset
uspto-grants-2015_11
Patent number
US09181272B2

Reaction notes

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