1,4-Dioxane → HCID 56932574, compound

HRID 1972524Notes

Reaction equation

HRID 1972524 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[S:6]([N:9]1[CH2:14][CH2:13][N:12]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([OH:30])([C:26]([F:29])([F:28])[F:27])[C:22]([F:25])([F:24])[F:23])=[CH:17][C:16]=2[C:31]#[C:32][CH2:33][NH:34]C(=O)OC(C)(C)C)[CH2:11][CH2:10]1)(=[O:8])=[O:7].[O:42]1CCOCC1>Cl>[F:27][C:26]([F:29])([F:28])[C:21]([OH:30])=[O:42].[NH2:34][CH2:33][C:32]#[C:31][C:16]1[CH:17]=[C:18]([C:21]([OH:30])([C:26]([F:28])([F:29])[F:27])[C:22]([F:23])([F:24])[F:25])[CH:19]=[CH:20][C:15]=1[N:12]1[CH2:13][CH2:14][N:9]([S:6]([C:2]2[S:1][CH:5]=[CH:4][CH:3]=2)(=[O:8])=[O:7])[CH2:10][CH2:11]1

Participants

4

Reactant 2

HCID 312751,4-DioxaneHCID 86670382HCID 86670382, compound

Product 1

HCID 56932574HCID 56932574, compound

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

A solution of tert-butyl 3-(5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-2-(4-(thiophen-2-ylsulfonyl)piperazin-1-yl)phenyl)prop-2-ynylcarbamate (698 mg, 1.11 mmol, Example 158) in 4 M HCl in dioxane (10 mL, 40 mmol) was stirred at room temperature for 30 min and then the solvent was removed under reduced pressure. The crude material was subjected to reverse-phase preparative HPLC using a Phenomenex Gemini C18 column (150×30 mm, 10 μm) eluting with 0.1% TFA in CH3CN/H2O (10% to 100% over 15 min) to 2-(3-(3-amino-1-propyn-1-yl)-4-(4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol trifluoroacetate as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.77 (s, 1H), 8.24 (br s, 3H), 8.10 (d, J=4.89 Hz, 1H), 7.70 (d, J=3.33 Hz, 1H), 7.56-7.64 (m, 2H), 7.32 (t, J=4.40 Hz, 1H), 7.14 (d, J=8.61 Hz, 1H), 4.01 (s, 2H), 3.27-3.33 (m, 4H), 3.10-3.20 (m, 4H); m/z (ESI, +ve ion) 528.1 (M+H)+. GK-GKRP IC50 (Binding)=1.919 μM.

Workup

  1. customthe solvent was removed under reduced pressure
  2. washeluting with 0.1% TFA in CH3CN/H2O (10% to 100% over 15 min) to 2-(3-(3-amino-1-propyn-1-yl)-4-(4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol trifluoroacetate as a white solid

Sources & evidence

ORD record
ord-da054221dad94058914cd60d4985f572
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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