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

HRID 1697465Notes

Reaction equation

HRID 1697465 reaction equation
[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

Participants

8

Reactant 5

HCID 81531Diisopropylethylamine2×HCID 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent2×

Procedure

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).

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-269433e933c04d5b8150acdac1a8f9d7
Source dataset
uspto-grants-2012_04
Patent number
US08163901B2

Reaction notes

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