Diisopropylethylamine → 6-Methoxy-1,2,3,4-tetrahydro-naphthalene-2-carboxylic acid [1-(2-fluoro-4-methanesulfonylamino-5-methyl-phenyl)-ethyl]-amide

HRID 1690788Notes

Reaction equation

HRID 1690788 reaction equation
[NH2:1][CH:2]([C:4]1[C:9]([F:10])=[CH:8][C:7]([NH:11][S:12]([CH3:15])(=[O:14])=[O:13])=[C:6]([CH3:16])[CH:5]=1)[CH3:3].[CH3:17][O:18][C:19]1[CH:20]=[C:21]2[C:26](=[CH:27][CH:28]=1)[CH2:25][CH:24]([C:29](O)=[O:30])[CH2:23][CH2:22]2.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.C([O-])(O)=O.[Na+]>CN(C)C=O>[F:10][C:9]1[CH:8]=[C:7]([NH:11][S:12]([CH3:15])(=[O:14])=[O:13])[C:6]([CH3:16])=[CH:5][C:4]=1[CH:2]([NH:1][C:29]([CH:24]1[CH2:23][CH2:22][C:21]2[C:26](=[CH:27][CH:28]=[C:19]([O:18][CH3:17])[CH:20]=2)[CH2:25]1)=[O:30])[CH3:3]

Participants

7

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 113562126-methoxy-1,2,3,4-tetrahydronaphthalene-2-carboxylic AcidHCID 58118636N-[4-(1-amino-ethyl)-5-fluoro-2-methyl-phenyl]-methanesulfonamide

Product 1

HCID 581186166-Methoxy-1,2,3,4-tetrahydro-naphthalene-2-carboxylic acid [1-(2-fluoro-4-methanesulfonylamino-5-methyl-phenyl)-ethyl]-amideYield 36.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

In a 20 ml vial, N-[4-(1-amino-ethyl)-5-fluoro-2-methyl-phenyl]-methanesulfonamide (100 mg, 0.4 mmol), 6-methoxy-1,2,3,4-tetrahydro-naphthalene-2-carboxylic acid (100 mg, 0.49 mmol) and N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (380 mg, 1.0 mmol) were dissolved in N,N-dimethylformamide (8 mL). N,N-Diisopropylethylamine (400 uL, 2.0 mmol) was added while stirring. The reaction was heated for 1 hour at 50° C. After cooling the reaction to room temperature, saturated NaHCO3 solution (20 ml) was poured into the vial and extracted with DCM (3×30 ml). The combined organics was washed once with brine (40 ml), dried over NaSO4, filtered and concentrated. Purification by HPLC yielded a solid (63.1 mg, 30%). m/z=435.2 (M+1). 1H-NMR (400 MHz, DMSO-d6) δ 9.24 (s, 1H), 8.34 (t, 1H, J=7.60 Hz), 7.21 (d, 1H, J=8.67 Hz), 7.06 (d, 1H, J=11.56 Hz), 7.00-6.97 (m, 1H), 6.68-6.62 (m, 2H), 5.11-5.06 (m, 1H), 3.68 (s, 3H), 3.00 (d, 31-1, J=0.97 Hz), 2.77-2.68 (m, 4H), 2.57-2.51 (m, 1H), 2.25 (s, 3H), 1.95-1.88 (m, 1H), 1.70-1.54 (m, 1H), 1.33 (d, 3H, J=7.13 Hz).

Workup

  1. temperatureAfter cooling
  2. customthe reaction to room temperature
  3. extractionextracted with DCM (3×30 ml)
  4. washThe combined organics was washed once with brine (40 ml)
  5. dry with materialdried over NaSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by HPLC

Sources & evidence

ORD record
ord-522b206b888b4ae2b59d6c53b5d3e35f
Source dataset
uspto-grants-2012_04
Patent number
US08153651B2

Reaction notes

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