Ethanolamine → HCID 67171544, compound

HRID 1506554Notes

Reaction equation

HRID 1506554 reaction equation
[OH:1][CH:2]([C:6]1[CH:7]=[C:8]2[C:31](=[CH:32][CH:33]=1)[C:12]1=[N:13][O:14][C:15]([C:16]3[C:20]([C:21]([F:24])([F:23])[F:22])=[C:19]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[O:18][N:17]=3)=[C:11]1[CH2:10][CH2:9]2)[C:3](O)=[O:4].[NH2:34][CH2:35][CH2:36][OH:37].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][CH:2]([C:6]1[CH:7]=[C:8]2[C:31](=[CH:32][CH:33]=1)[C:12]1=[N:13][O:14][C:15]([C:16]3[C:20]([C:21]([F:22])([F:24])[F:23])=[C:19]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[O:18][N:17]=3)=[C:11]1[CH2:10][CH2:9]2)[C:3]([NH:34][CH2:35][CH2:36][OH:37])=[O:4]

Participants

7

Reactant 4

HCID 700EthanolamineHCID 79724-MethylmorpholineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 67170876HCID 67170876, compound

Product 1

HCID 67171544HCID 67171544, compoundYield 65.5%

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)acetic acid (Preparation 131B, isomer 2, 25 mg, 0.055 mmol) in DMF (1 mL) was added 2-aminoethanol (5.02 mg, 0.082 mmol), BOP (31.5 mg, 0.071 mmol), and 4-methylmorpholine (33.2 mg, 0.329 mmol). The reaction mixture was stirred for 30 min. Methanol was added and it was purified by prep HPLC (Phenomenex 21.2×250 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 30 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)acetamide (18 mg, 0.036 mmol, 65.3% yield) as a white solid: product HPLC ret. time=8.66 min (condition G); LC/MS M+1=500.04; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.96 (1H, t, J=5.72 Hz), 7.87 (1H, d, J=7.92 Hz), 7.80 (2H, d, J=7.26 Hz), 7.63-7.76 (3H, m), 7.44-7.53 (2H, m), 6.34 (1H, d, J=4.84 Hz), 4.98 (1H, d, J=4.62 Hz), 4.71 (1H, t, J=5.50 Hz), 3.43 (2H, q, J=5.94 Hz), 3.11-3.24 (2H, m), 3.04 (4H, s).

Workup

  1. customit was purified by prep HPLC (Phenomenex 21.2×250 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 30 min, 20 mL/min, 220 nM)

Sources & evidence

ORD record
ord-a69b4f1d8d2b400899954e25e93bd5d5
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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