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

HRID 1697466ノート

反応式

HRID 1697466 の反応式
[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

参加物

8

反応物 5

HCID 81531Diisopropylethylamine2 回HCID 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6342Acetonitrile溶媒2 回

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-29306fb14147422e9d00d51610e53cee
出典データセット
uspto-grants-2012_04
特許番号
US08163901B2

反応ノート

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