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

HRID 1697466Notes

Reaction equation

HRID 1697466 reaction equation
[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

Participants

8

Reactant 5

HCID 81531Diisopropylethylamine2×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

Product 1

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

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolvent2×

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-29306fb14147422e9d00d51610e53cee
Source dataset
uspto-grants-2012_04
Patent number
US08163901B2

Reaction notes

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