Diisopropylethylamine → 6-Trifluoromethoxy-2H-chromene-3-carboxylic acid (quinolin-4-ylmethyl)-amide

HRID 1697466노트

반응식

HRID 1697466 반응식
[F:1][C:2]([F:18])([F:17])[O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[O:10][CH2:9][C:8]([C:14]([OH:16])=O)=[CH:7]2.F[P-](F)(F)(F)(F)F.[CH3:26][N+:27](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.CCN(C(C)C)C(C)C.Cl.Cl.[N:54]1[C:63]2[C:58](=[CH:59][CH:60]=[CH:61][CH:62]=2)[C:57](NC)=[CH:56][CH:55]=1.C([O-])(O)=O.[Na+]>CN(C)C1C=CN=CC=1.CC#N>[N:54]1[C:63]2[C:58](=[CH:59][CH:60]=[CH:61][CH:62]=2)[C:57]([CH2:26][NH:27][C:14]([C:8]2[CH2:9][O:10][C:11]3[C:6]([CH:7]=2)=[CH:5][C:4]([O:3][C:2]([F:1])([F:18])[F:17])=[CH:13][CH:12]=3)=[O:16])=[CH:56][CH:55]=1

참가 물질

8

반응물 5

HCID 81531Diisopropylethylamine2회HCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 581254866-Trifluoromethoxy-2H-chromene-3-carboxylic acidHCID 66943123N-methylquinolin-4-amine;dihydrochloride

생성물 1

HCID 441944876-Trifluoromethoxy-2H-chromene-3-carboxylic acid (quinolin-4-ylmethyl)-amide수율 9.8%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6342Acetonitrile용매2회

실험 절차

To a vial containing 6-trifluoromethoxy-2H-chromene-3-carboxylic acid (42 mg, 0.16 mmol) was added a solution containing N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (67.5 mg, 0.18 mmol), DIPEA (2.4 eq), and 4-dimethylaminopyridine (1.97 mg, 0.016 mmol) in anhydrous MeCN (3 mL). After stirring for 5 minutes, a solution of quinolin-4-yl-methylamine dihydrochloride (41 mg, 0.18 mmol) and DIPEA (2.4 eq) in anhydrous MeCN (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 3% MeOH in DCM over 40 minutes) gave the product (6.3 mg) as a solid. m/z=401.4 (M+1), r.t.=2.76 mins. 1H NMR (400 MHz; DMSO-d6) δ 9.00 (1H, t), 8.86 (1H, d), 8.21 (1H, d), 8.06 (1H, d), 7.79 (1H, t), 7.67 (1H, t), 7.43 (1H, d), 7.37 (1H, s), 7.32 (1H, s), 7.25 (1H, d), 6.97 (1H, d), 5.03 (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-29306fb14147422e9d00d51610e53cee
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08163901B2

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