Pyridine → N,N-dimethyl-2-morpholino-4-oxo-8-(1-(3,4,5-trifluorophenylamino)ethyl)-4H-chromene-6-carboxamide

HRID 1187242노트

반응식

HRID 1187242 반응식
[NH2:1][CH:2]([C:4]1[CH:5]=[C:6]([C:21]([N:23]([CH3:25])[CH3:24])=[O:22])[CH:7]=[C:8]2[C:13]=1[O:12][C:11]([N:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1)=[CH:10][C:9]2=[O:20])[CH3:3].[F:26][C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[C:31]([F:34])[C:32]=1[F:33].ClC(Cl)C.N1C=CC=CC=1>C(Cl)Cl.O.C(O[Cu]OC(=O)C)(=O)C>[CH3:25][N:23]([CH3:24])[C:21]([C:6]1[CH:7]=[C:8]2[C:13](=[C:4]([CH:2]([NH:1][C:29]3[CH:28]=[C:27]([F:26])[C:32]([F:33])=[C:31]([F:34])[CH:30]=3)[CH3:3])[CH:5]=1)[O:12][C:11]([N:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1)=[CH:10][C:9]2=[O:20])=[O:22]

참가 물질

7

반응물 4

HCID 1049PyridineHCID 63651,1-DichloroethaneHCID 2734671(3,4,5-Trifluorophenyl)boronic Acid (contains varying amounts of Anhydride)HCID 582349768-(1-aminoethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide

생성물 1

HCID 52913705N,N-dimethyl-2-morpholino-4-oxo-8-(1-(3,4,5-trifluorophenylamino)ethyl)-4H-chromene-6-carboxamide

시약·촉매·용매 2

HCID 178476682HCID 178476682, 화합물촉매HCID 6344Dichloromethane용매

실험 절차

8-(1-aminoethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (232 mg, 0.67 mmol, [α]D20°: +35° in acetonitrile), 3,4,5-trifluorophenylboronic acid (236 mg, 1.34 mmol), diacetoxycopper hydrate (148 mg, 0.74 mmol) and molecular sieves 4A (1 g) were weighed out in a flask. Dichloroethane (4 mL) then pyridine (0.109 mL, 1.34 mmol) were added and the resulting mixture was stirred at RT for 2 days under an oxygen atmosphere. The mixture was diluted with DCM, filtered through a pad of celite, the filtrate was washed with a 0.5N NaOH aq. sol. and the aqueous phase extracted with DCM. The combined organics were dried over magnesium sulphate and concentrated down. The crude product was purified by flash chromatography on silica gel eluting with 0 to 10% MeOH in ethyl acetate/DCM (1:1). The solvent was evaporated to dryness to afford N,N-dimethyl-2-morpholino-4-oxo-8-(1-(3,4,5-trifluorophenylamino)ethyl)-4H-chromene-6-carboxamide single enantiomer (100 mg, 31%) as a white foam. Mass Spectrum: M+H 476. [α]D20°: −108° in MeCN. NMR Spectrum (CDCl3): 1.56 (d, 3H), 2.91 (s, 3H), 3.09 (s, 3H), 3.47-3.56 (m, 4H), 3.82-3.90 (m, 4H), 4.35 (d, 1H), 4.79-4.88 (m, 1H), 5.56 (s, 1H), 6.03 (dd, 2H), 7.70 (d, 1H), 8.12 (d, 1H).

후처리

  1. filtrationfiltered through a pad of celite
  2. washthe filtrate was washed with a 0.5N NaOH aq. sol.
  3. extractionthe aqueous phase extracted with DCM
  4. dry with materialThe combined organics were dried over magnesium sulphate
  5. concentrationconcentrated down
  6. customThe crude product was purified by flash chromatography on silica gel eluting with 0 to 10% MeOH in ethyl acetate/DCM (1:1)
  7. customThe solvent was evaporated to dryness

출처 및 근거

ORD 기록
ord-dbceddca3f8246c18339fd4914d56256
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08673906B2

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