Diisopropylethylamine → HCID 58118621, compound

HRID 1690807Notes

Reaction equation

HRID 1690807 reaction equation
Cl.[NH2:2][C@@H:3]([C:5]1[C:10]([F:11])=[CH:9][C:8]([NH:12][S:13]([CH3:16])(=[O:15])=[O:14])=[C:7]([CH3:17])[CH:6]=1)[CH3:4].[F:18][C:19]([F:34])([F:33])[C:20]1[N:25]=[C:24]2[O:26][CH2:27][CH:28]([C:30](O)=[O:31])[O:29][C:23]2=[CH:22][CH:21]=1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C([O-])(O)=O.[Na+]>CN(C)C1C=CN=CC=1.CN(C=O)C>[F:11][C:10]1[CH:9]=[C:8]([NH:12][S:13]([CH3:16])(=[O:15])=[O:14])[C:7]([CH3:17])=[CH:6][C:5]=1[C@H:3]([NH:2][C:30]([CH:28]1[CH2:27][O:26][C:24]2=[N:25][C:20]([C:19]([F:33])([F:18])[F:34])=[CH:21][CH:22]=[C:23]2[O:29]1)=[O:31])[CH3:4]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 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 hydrochlorideHCID 66718692HCID 66718692, compound

Product 1

HCID 58118621HCID 58118621, compoundYield 62.8%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of N-[4-((R)-1-Aminoethyl)-5-fluoro-2-methylphenyl]methanesulfonamide hydrochloride (25 mg, 0.09 mmol), 6-trifluoromethyl-2,3-dihydro[1,4]dioxino[2,3-b]pyridine-2-carboxylic acid (20 mg, 0.08 mmol), 4-dimethylaminopyridine (0.8 mg, 0.8 mop and N,N-diisopropylethylamine (50 μL, 0.29 mmol) in anhydrous DMF (1 mL) was added HATU (34 mg, 0.09 mmol). The reaction was stirred overnight at room temperature, then poured into saturated NaHCO3 solution (20 mL) and extracted with EtOAc (3×20 mL). The combined organics were washed with brine (3×30 mL), dried (MgSO4), filtered and concentrated. Flash chromatography (0 to 3.5% MeOH in DCM) gave the title compound (24 mg, 60%) as a solid. m/z=478.2 (M+1), r.t.=2.98 mins. 1H NMR (400 MHz; DMSO-d6) 9.20 (1H, dd), 8.82 (1H, dd), 7.51-7.43 (2H, m), 7.27 (0.5H, d), 7.14 (0.5H, d), 7.07 (1H, dd), 5.20-5.17 (1H, m), 5.09 (1H, t), 4.48-4.42 (2H, m), 3.01 (3H, d), 2.27 (1.5H, s), 2.21 (1.5H, s), 1.38 (3H, d).

Workup

  1. extractionextracted with EtOAc (3×20 mL)
  2. washThe combined organics were washed with brine (3×30 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-140f8451534a452481bd0b9fc0ce9ada
Source dataset
uspto-grants-2012_04
Patent number
US08153651B2

Reaction notes

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