Ethanolamine → HCID 67170738, compound

HRID 1506548Notes

Reaction equation

HRID 1506548 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](O)=[O:4].[NH2:28][CH2:29][CH2:30][OH:31].CN1CCOCC1.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:28][CH2:29][CH2:30][OH:31])=[O:4]

Participants

6

Reactant 4

HCID 700EthanolamineHCID 79724-MethylmorpholineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 67170951HCID 67170951, compound

Product 1

HCID 67170738HCID 67170738, compoundYield 67.4%

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, 18 mg, 0.050 mmol) in DMF (1 mL) was added 2-aminoethanol (5.45 mg, 0.089 mmol), 4-methylmorpholine (0.033 mL, 0.29 mmol) and BOP (39.4 mg, 0.089 mmol). The reaction mixture was stirred overnight and was then purified by preparative HPLC (Phenomenex Luna 5 u C18 21.2×100 mm, Solvent A: 90% water with 10% MeOH and 0.1% TFA, Solvent B: 90% MeOH with 10% water and 0.1% TFA, Gradient: 0% B to 100% B over 10 min, 20 mL/min, 220 nM, product retention time=11.9 min) to give 2-hydroxy-N-(2-hydroxyethyl)-2-(3-(4-propylphenyl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)acetamide (14.5 mg, 0.033 mmol, 67.4% yield): product HPLC ret. time=8.79 min. (condition G); LC/MS M+1=407.1; 1H NMR (400 MHz, CD3OD) δ ppm 7.87 (1H, d, J=7.92 Hz), 7.72 (2H, d, J=8.36 Hz), 7.44-7.55 (2H, m), 7.37 (2H, d, J=8.36 Hz), 5.07 (1H, s), 3.58-3.69 (2H, m), 3.34-3.43 (2H, m), 3.05 (4H, s), 2.59-2.74 (2H, m), 1.61-1.80 (2H, m), 0.97 (3H, t, J=7.37 Hz).

Workup

  1. customwas then purified by preparative HPLC (Phenomenex Luna 5 u C18 21.2×100 mm, Solvent A: 90% water with 10% MeOH and 0.1% TFA, Solvent B: 90% MeOH with 10% water and 0.1% TFA, Gradient: 0% B to 100% B over 10 min, 20 mL/min, 220 nM, product retention time=11.9 min)

Sources & evidence

ORD record
ord-ae252a5655ca4a599e3dca807a19fc30
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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