Diisopropylethylamine → (R)-N-(1-(2-Fluoro-5-methyl-4-(methylsulfonamido)phenyl)ethyl)-2h-chromene-3-carboxamide

HRID 1690782Notes

Reaction equation

HRID 1690782 reaction equation
[O:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([C:11]([OH:13])=O)[CH2:2]1.Cl.[NH2:15][C@@H:16]([C:18]1[C:23]([F:24])=[CH:22][C:21]([NH:25][S:26]([CH3:29])(=[O:28])=[O:27])=[C:20]([CH3:30])[CH:19]=1)[CH3:17].F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C)C=O.O1CCCC1>[F:24][C:23]1[CH:22]=[C:21]([NH:25][S:26]([CH3:29])(=[O:28])=[O:27])[C:20]([CH3:30])=[CH:19][C:18]=1[C@H:16]([NH:15][C:11]([C:3]1[CH2:2][O:1][C:10]2[C:5]([CH:4]=1)=[CH:6][CH:7]=[CH:8][CH:9]=2)=[O:13])[CH3:17]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 3223042H-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 66718598(R)-N-(4-(1-aminoethyl)-5-fluoro-2-methylphenyl)methanesulfonamide hydrochloride

Product 1

HCID 58118638(R)-N-(1-(2-Fluoro-5-methyl-4-(methylsulfonamido)phenyl)ethyl)-2h-chromene-3-carboxamideYield 38.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2H-chromene-3-carboxylic acid (0.015 g, 0.085 mmol), N-[4-((R)-1-aminoethyl)-5-fluoro-2-methylphenyl]methanesulfonamide hydrochloride (20.00 mg, 0.07 mmol) and N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (0.032 g, 0.085 mmol) in N,N-dimethylformamide (0.39 g) was added N,N-diisopropylethylamine (0.046 g, 0.35 mmol). Tetrahydrofuran (0.38 g) was added to dilute solution. The reaction was stirred overnight. It was then concentrated and purified by HPLC to obtain the product (10.8 mg, 37%) a solid. m/z=405.1 (M+1). 1H-NMR (400 MHz, DMSO-d) δ 9.19 (s, 1H), 8.61 (d, 1H, J=7.66 Hz), 7.37 (s, 1H), 7.30-7.21 (m, 3H), 7.07 (d, 1H, J=11.41 Hz), 6.96 (dt, 1H, J=7.54 Hz), 6.84 (d, 1H, J=7.81 Hz), 5.25-5.18 (m, 1H), 4.88 (s, 2H), 3.02 (s, 3H), 2.25 (s, 3H), 1.41 (d, 3H, J=7.07 Hz).

Workup

  1. concentrationIt was then concentrated
  2. custompurified by HPLC

Sources & evidence

ORD record
ord-4535119cbbdf426bb04f1d5cd0b03595
Source dataset
uspto-grants-2012_04
Patent number
US08153651B2

Reaction notes

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