Diisopropylethylamine → tert-butyl 5-((7-fluoro-1,1-dimethyl-2,3-dihydro-1H-inden-5-yl)carbamoyl)-2-methoxy-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate

HRID 2202238Notes

Reaction equation

HRID 2202238 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]([NH2:53])[CH:45]=[C:46]2[C:50]=1[C:49]([CH3:52])([CH3:51])[CH2:48][CH2:47]2.CCN(C(C)C)C(C)C>CN(C1C=CN=CC=1)C.C(OCC)(=O)C.O>[F:41][C:42]1[CH:43]=[C:44]([NH:53][C:38]([CH:27]2[N:26]([C:24]([O:23][C:19]([CH3:21])([CH3:20])[CH3:22])=[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:45]=[C:46]2[C:50]=1[C:49]([CH3:51])([CH3:52])[CH2:48][CH2:47]2

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 1186227506-tert-butoxycarbonyl-2-methoxy-7,8-dihydro-5H-1,6-naphthyridine-5-carboxylic acidHCID 1186227997-fluoro-1,1-dimethyl-2,3-dihydro-1H-inden-5-amine

Product 1

HCID 118622788tert-butyl 5-((7-fluoro-1,1-dimethyl-2,3-dihydro-1H-inden-5-yl)carbamoyl)-2-methoxy-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylateYield 81.2%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
65 °C

Procedure

T3P (4.89 mL, 8.22 mmol) was added to a solution of 6-(tert-butoxycarbonyl)-2-methoxy-5,6,7,8-tetrahydro-1,6-naphthyridine-5-carboxylic acid (1.69 g, 5.48 mmol), 7-fluoro-1,1-dimethyl-2,3-dihydro-1H-inden-5-amine (0.982 g, 5.48 mmol), DIEA (4.77 mL, 27.41 mmol) and DMAP (0.737 g, 6.03 mmol) in ethyl acetate (40 mL) at room temperature. The mixture was stirred at 65° C. for 15 hr, the reaction mixture was poured into water (150 mL), and the mixture was extracted with ethyl acetate (×3). The organic layer was washed with 10% aqueous citric acid solution, aqueous sodium hydrogencarbonate solution, water and brine, and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained precipitate was washed with hexane to give tert-butyl 5-((7-fluoro-1,1-dimethyl-2,3-dihydro-1H-inden-5-yl)carbamoyl)-2-methoxy-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate (2.09 g, 4.45 mmol, 81%) as an off-white powder.

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, water and brine
  3. dry with materialdried over magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. washThe obtained precipitate was washed with hexane

Sources & evidence

ORD record
ord-f01f0ebc394b4308a29e439ac93090e2
Source dataset
uspto-grants-2016_06
Patent number
US09365520B2

Reaction notes

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