Ethanolamine → HCID 67172602, compound

HRID 1506561Notes

Reaction equation

HRID 1506561 reaction equation
[OH:1][C:2]([C:7]1[CH:8]=[C:9]2[C:32](=[CH:33][CH:34]=1)[C:13]1=[N:14][O:15][C:16]([C:17]3[C:21]([C:22]([F:25])([F:24])[F:23])=[C:20]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[O:19][N:18]=3)=[C:12]1[CH2:11][CH2:10]2)([CH3:6])[C:3]([OH:5])=O.[NH2:35][CH2:36][CH2:37][OH:38].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CN1CCOCC1>CN(C=O)C.CO>[OH:1][C:2]([C:7]1[CH:8]=[C:9]2[C:32](=[CH:33][CH:34]=1)[C:13]1=[N:14][O:15][C:16]([C:17]3[C:21]([C:22]([F:23])([F:25])[F:24])=[C:20]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[O:19][N:18]=3)=[C:12]1[CH2:11][CH2:10]2)([CH3:6])[C:3]([NH:35][CH2:36][CH2:37][OH:38])=[O:5]

Participants

7

Reactant 4

HCID 700EthanolamineHCID 79724-MethylmorpholineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 67171061HCID 67171061, compound

Product 1

HCID 67172602HCID 67172602, compoundYield 29.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

To 2-hydroxy-2-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)propanoic acid (Preparation 134D, isomer 1, 15 mg, 0.032 mmol) in DMF (1 mL) was added 2-aminoethanol (2.9 mg, 0.048 mmol), BOP (18.3 mg, 0.041 mmol) and 4-methylmorpholine (12.9 mg, 0.13 mmol). The reaction mixture was stirred for 1 h. Methanol was added and it was purified by prep HPLC (Phenomenex Luna 5 u 21.2×100 mm, Solvent A: 90% water with 10% acetonitrile and 0.1% TFA, Solvent B: 90% acetonitrile with 10% water and 0.1% TFA, Gradient: 0% B to 100% B over 10 min, 20 mL/min, 220 nM) to yield 2-hydroxy-N-(2-hydroxyethyl)-2-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)propanamide (5 mg, 9.45 μmol, 29.6% yield): product HPLC ret. time=9.07 min (condition G); LC/MS M+1=514.16; 1H NMR (400 MHz, CD3OD) δ ppm 7.91 (1H, d, J=7.92 Hz), 7.77 (2H, d, J=7.26 Hz), 7.58-7.71 (5H, m), 3.60 (2H, td, J=5.72, 3.30 Hz), 3.33-3.41 (2H, m), 3.07 (4H, s), 1.78 (3H, s).

Workup

  1. customit was purified by prep HPLC (Phenomenex Luna 5 u 21.2×100 mm, Solvent A: 90% water with 10% acetonitrile and 0.1% TFA, Solvent B: 90% acetonitrile with 10% water and 0.1% TFA, Gradient: 0% B to 100% B over 10 min, 20 mL/min, 220 nM)

Sources & evidence

ORD record
ord-4829d323b7774f5d9fbc49e56218fa63
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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