4-Methylmorpholine → HCID 67170576, compound

HRID 1506549Notes

Reaction equation

HRID 1506549 reaction equation
[OH:1][CH:2]([C:6]1[CH:7]=[C:8]2[C:25](=[CH:26][CH:27]=1)[C:12]1=[N:13][O:14][C:15]([C:16]3[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][CH3:24])=[CH:18][CH:17]=3)=[C:11]1[CH2:10][CH2:9]2)[C:3]([OH:5])=O.CN1CCOCC1.Cl.[NH2:36][CH2:37][CH2:38][S:39]([CH3:42])(=[O:41])=[O:40].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C=O)C>[OH:1][CH:2]([C:6]1[CH:7]=[C:8]2[C:25](=[CH:26][CH:27]=1)[C:12]1=[N:13][O:14][C:15]([C:16]3[CH:17]=[CH:18][C:19]([CH2:22][CH2:23][CH3:24])=[CH:20][CH:21]=3)=[C:11]1[CH2:10][CH2:9]2)[C:3]([NH:36][CH2:37][CH2:38][S:39]([CH3:42])(=[O:41])=[O:40])=[O:5]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 17749886Ethanamine, 2-(methylsulfonyl)-, hydrochloride (1:1)HCID 67170951HCID 67170951, compound

Product 1

HCID 67170576HCID 67170576, compoundYield 18.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-hydroxy-2-(3-(4-propylphenyl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)acetic acid (example 127, 35 mg, 0.096 mmol) in DMF (1 mL) was added 4-methylmorpholine (0.064 mL, 0.58 mmol), 2-aminoethylmethylsulfone hydrochloride (27.7 mg, 0.17 mmol), and BOP (77 mg, 0.17 mmol). The reaction mixture was stirred overnight and was then purified by preparative HPLC (Column: Waters XBridge C18, 19×250 mm, 5-μm particles; Guard Column: Waters XBridge C18, 19×10 mm, 5-μm particles; Mobile Phase A: 5:95 methanol:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 methanol:water with 10-mM ammonium acetate; Gradient: 45-100% B over 25 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min). Fractions containing the desired product were combined and dried via centrifugal evaporation to give 2-hydroxy-N-(2-(methylsulfonyl)ethyl)-2-(3-(4-propylphenyl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)acetamide (8.3 mg, 0.018 mmol, 18.4% yield): product HPLC ret. time=2.54 min. (condition F); LC/MS M+1=468; 1H NMR (400 MHz, 1:1 CD3OD and CDCl3) δ ppm 7.87 (1H, d, J=8.36 Hz), 7.67 (2H, d, J=8.14 Hz), 7.40-7.50 (2H, m), 7.31 (2H, d, J=8.36 Hz), 5.06 (1H, s), 3.73 (2H, t, J=6.49 Hz), 3.19-3.30 (2H, m), 2.94 (3H, s), 2.57-2.70 (2H, m), 1.60-1.77 (2H, m), 0.94 (3H, t, J=7.37 Hz).

Workup

  1. customwas then purified by preparative HPLC (Column
  2. waitGradient: 45-100% B over 25 minutes
  3. customa 5-minute hold
  4. additionFractions containing the desired product
  5. customdried via centrifugal evaporation

Sources & evidence

ORD record
ord-44a30e9fc3cf4bc0858c6cd16b85f72e
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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