Diisopropylethylamine → 6-Chloro-2H-chromene-3-carboxylic acid (Quinolin-4-ylmethyl)-amide

HRID 1697465노트

반응식

HRID 1697465 반응식
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][CH2:7][C:6]([C:12]([OH:14])=O)=[CH:5]2.F[P-](F)(F)(F)(F)F.[CH3:22][N+:23](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.CCN(C(C)C)C(C)C.Cl.Cl.[N:50]1[C:59]2[C:54](=[CH:55][CH:56]=[CH:57][CH:58]=2)[C:53](NC)=[CH:52][CH:51]=1.C([O-])(O)=O.[Na+]>CN(C)C1C=CN=CC=1.CN(C=O)C>[N:50]1[C:59]2[C:54](=[CH:55][CH:56]=[CH:57][CH:58]=2)[C:53]([CH2:22][NH:23][C:12]([C:6]2[CH2:7][O:8][C:9]3[C:4]([CH:5]=2)=[CH:3][C:2]([Cl:1])=[CH:11][CH:10]=3)=[O:14])=[CH:52][CH:51]=1

참가 물질

8

반응물 5

HCID 81531Diisopropylethylamine2회HCID 516892Sodium BicarbonateHCID 5969296-chloro-2H-chromene-3-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66943123N-methylquinolin-4-amine;dihydrochloride

생성물 1

HCID 441943926-Chloro-2H-chromene-3-carboxylic acid (Quinolin-4-ylmethyl)-amide수율 37.6%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6228Dimethylformamide용매2회

실험 절차

To a vial containing 6-chloro-2H-chromene-3-carboxylic acid (43.74 mg, 0.21 mmol) was added a solution containing N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (79 mg, 0.21 mmol), DIPEA (2.4 eq), and 4-dimethylaminopyridine (2.1 mg, 0.017 mmol) in anhydrous DMF (3 mL). After stirring for 5 minutes, a solution of quinolin-4-yl-methylamine dihydrochloride (40 mg, 0.2 mmol) and DIPEA (2.4 eq) in anhydrous DMF (2 mL) was added. The reaction was stirred overnight at room temperature. The reaction mixture was poured into saturated NaHCO3 solution (50 mL) and extracted with EtOAc (3×50 mL). The combined organics were washed with brine (3×50 mL), dried (MgSO4), filtered and concentrated. Flash chromatography (0 to 4% MeOH in DCM over 30 minutes) gave the product (26.4 mg) as a solid. m/z=350.8 (M+1), r.t.=2.26 mins. 1H NMR (400 MHz; DMSO-d6) δ 8.99 (1H, t), 8.86 (1H, d), 8.20 (1H, dd), 8.06 (1H, dd), 7.79 (1H, t), 7.67 (1H, t), 7.42 (1H, d), 7.34 (2H, d), 7.27 (1H, dd), 6.90 (1H, d), 5.00 (2H, s), 4.90 (2H, d).

후처리

  1. additionwas added a solution
  2. stirringThe reaction was stirred overnight at room temperature
  3. extractionextracted with EtOAc (3×50 mL)
  4. washThe combined organics were washed with brine (3×50 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated

출처 및 근거

ORD 기록
ord-269433e933c04d5b8150acdac1a8f9d7
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08163901B2

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