Ethanolamine → HCID 67168446, compound

HRID 1506487Notes

Reaction equation

HRID 1506487 reaction equation
[OH:1][CH:2]([C:6]1[CH:7]=[C:8]2[C:16](=[CH:17][CH:18]=1)[C:15]1[S:14][C:13]([C:19]3[O:23][N:22]=[C:21]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[C:20]=3[C:30]([F:33])([F:32])[F:31])=[N:12][C:11]=1[CH2:10][CH2:9]2)[C:3]([OH:5])=O.C[N:35]1CC[O:38][CH2:37][CH2:36]1.NCCO.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(O)(C(F)(F)F)=O>CN(C=O)C.CO.O>[OH:1][CH:2]([C:6]1[CH:7]=[C:8]2[C:16](=[CH:17][CH:18]=1)[C:15]1[S:14][C:13]([C:19]3[O:23][N:22]=[C:21]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[C:20]=3[C:30]([F:33])([F:31])[F:32])=[N:12][C:11]=1[CH2:10][CH2:9]2)[C:3]([NH:35][CH2:36][CH2:37][OH:38])=[O:5]

Participants

9

Reactant 5

HCID 700EthanolamineHCID 6422Trifluoroacetic acid2×HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67170811HCID 67170811, compound

Product 1

HCID 67168446HCID 67168446, compoundYield 34.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent3×HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Procedure

To 2-hydroxy-2-(2-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydronaphtho[2,1-d]thiazol-7-yl)acetic acid (Preparation 84C, isomer 1, 0.033 g, 0.070 mmol) in DMF (1 mL) were sequentially added N-methylmorpholine (0.031 mL, 0.279 mmol), 2-aminoethanol (5.48 μl, 0.091 mmol) and HATU (0.040 g, 0.105 mmol) at room temperature. The reaction mixture was stirred at room temperature for 18 h. The reaction mixture was diluted with 0.5 mL of MeOH and subjected to preparative. HPLC (Waters Xbridge C18 19×100 mm; solvent A: 10% MeOH, 90% H2O, 0.1% TFA; Solvent B: 90% MeOH, 10% H2O, 0.1% TFA). The desired fractions were collected, concentrated and freeze dried using MeOH (0.3 mL) and water (0.7 mL) to yield 2-hydroxy-N-(2-hydroxyethyl)-2-(2-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydronaphtho[2,1-d]thiazol-7-yl)acetamide (0.013 g, 0.024 mmol, 34.3% yield) as a pale yellow solid. The compound had an HPLC retention time=3.54 min. (condition C); LC/MS M+1=516; 1H NMR (500 MHz, CDCl3) δ ppm 7.65 (2H, d, J=6.9 Hz), 7.48-7.58 (3H, m), 7.33-7.44 (3H, m), 6.72 (1H, br. s.), 5.12 (1H, s), 3.76 (2H, t, J=4.9 Hz), 3.46-3.53 (2H, m), 3.12-3.25 (4H, m).

Workup

  1. customat room temperature
  2. customThe desired fractions were collected
  3. concentrationconcentrated
  4. customfreeze dried

Sources & evidence

ORD record
ord-5bc7df4b96f343f38bf9c1e3039bd162
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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