Diisopropylethylamine → tert-butyl 5-((3,5-difluoro-4-(trimethylsilyl)phenyl)carbamoyl)-2-methoxy-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate

HRID 2202266Notes

Reaction equation

HRID 2202266 reaction equation
C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.[C:19]([O:23][C:24]([N:26]1[CH2:35][CH2:34][C:33]2[N:32]=[C:31]([O:36][CH3:37])[CH:30]=[CH:29][C:28]=2[CH:27]1[C:38]([OH:40])=O)=[O:25])([CH3:22])([CH3:21])[CH3:20].[F:41][C:42]1[CH:43]=[C:44]([CH:46]=[C:47]([F:53])[C:48]=1[Si:49]([CH3:52])([CH3:51])[CH3:50])[NH2:45].CCN(C(C)C)C(C)C>CN(C1C=CN=CC=1)C.C(OCC)(=O)C.O>[F:53][C:47]1[CH:46]=[C:44]([NH:45][C:38]([CH:27]2[N:26]([C:24]([O:23][C:19]([CH3:20])([CH3:22])[CH3:21])=[O:25])[CH2:35][CH2:34][C:33]3[N:32]=[C:31]([O:36][CH3:37])[CH:30]=[CH:29][C:28]2=3)=[O:40])[CH:43]=[C:42]([F:41])[C:48]=1[Si:49]([CH3:50])([CH3:51])[CH3:52]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 1186227506-tert-butoxycarbonyl-2-methoxy-7,8-dihydro-5H-1,6-naphthyridine-5-carboxylic acidHCID 1254649723,5-Difluoro-4-(trimethylsilyl)aniline

Product 1

HCID 131735739tert-butyl 5-((3,5-difluoro-4-(trimethylsilyl)phenyl)carbamoyl)-2-methoxy-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylateYield 80%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

T3P (3.84 mL, 6.45 mmol) was added to a solution of 6-(tert-butoxycarbonyl)-2-methoxy-5,6,7,8-tetrahydro-1,6-naphthyridine-5-carboxylic acid (1.326 g, 4.3 mmol), 3,5-difluoro-4-(trimethylsilyl)aniline (0.866 g, 4.30 mmol), DIEA (3.74 mL, 21.50 mmol) and DMAP (0.578 g, 4.73 mmol) in ethyl acetate (31 mL) at room temperature, and the mixture was stirred at 65° C. for 15 hr. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate (×3). The organic layer was washed with 10% aqueous citric acid solution, aqueous sodium hydrogencarbonate solution and brine, and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The precipitate was washed with cooled hexane to give tert-butyl 5-((3,5-difluoro-4-(trimethylsilyl)phenyl)carbamoyl)-2-methoxy-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate (1.69 g, 3.44 mmol, 80%) as white crystals.

Workup

  1. extractionthe mixture was extracted with ethyl acetate (×3)
  2. washThe organic layer was washed with 10% aqueous citric acid solution, aqueous sodium hydrogencarbonate solution and brine
  3. dry with materialdried over magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. washThe precipitate was washed with cooled hexane

Sources & evidence

ORD record
ord-38548372ffb74d5a95131c51bed10940
Source dataset
uspto-grants-2016_06
Patent number
US09365520B2

Reaction notes

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