Hydrochloric Acid → HCID 22280169, compound

HRID 1591563Notes

Reaction equation

HRID 1591563 reaction equation
C[O:2][C:3](=[O:38])[CH2:4][O:5][C:6]1[CH:11]=[C:10]([O:12][CH3:13])[C:9]([S:14][CH2:15][CH2:16][C:17]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[N:19]([CH2:26][C:27]3[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][CH:28]=3)[CH:18]=2)=[CH:8][C:7]=1[CH3:37].COC(=O)COC1C=C(OC)C(SCCC2C3C(=CC=CC=3)NC=2)=CC=1C.[H-].[Na+].FC(F)(F)C1C=CC(CBr)=CC=1.Cl>CN(C=O)C>[CH3:13][O:12][C:10]1[C:9]([S:14][CH2:15][CH2:16][C:17]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[N:19]([CH2:26][C:27]3[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:34])[F:35])=[CH:29][CH:28]=3)[CH:18]=2)=[CH:8][C:7]([CH3:37])=[C:6]([CH:11]=1)[O:5][CH2:4][C:3]([OH:38])=[O:2]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 1230621-(Bromomethyl)-4-(trifluoromethyl)benzeneHCID 20827018HCID 20827018, compoundHCID 20827043HCID 20827043, compound2×

Product 1

HCID 22280169HCID 22280169, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Preparation of {4-[2-(1H-Indol-3-yl)-ethylsulfanyl]-5-methoxy-2-methyl-phenoxy}-acetic acid methyl ester (compound 54A) The compound 1D (1.622 g, 6.7 mmol) and 3-(2-bromo-ethyl)-1H-indole (1.50 g, 6.69 mmol) was dissolved in 5 ml DMF. Potassium carbonate (1.11 g, 8.03 mmol) was added followed by stirring at room temperature for 3 h. The reaction was filtered, concentrated and purified by MPLC to give the title compound. MS m/z 225 (M+1). Step 2. Preparation of (5-Methoxy-2-methyl-4-{2-[1-(4-trifluoromethyl-benzyl)-1H-indol-3-yl]-ethylsulfanyl}-phenoxy)-acetic acid methyl ester (compound 54B) The compound 54A (0.300 g, 0.778 mmol) was dissolved in 5 ml DMF. NaH was added and stirred for ½ h. 4-trifluoromethylbenzyl bromide (0.223 g, 0.934 mmol) was added and the reaction was stirred for 1.5 h. 10 ml 2N HCl was added to pH<4. The DMF solution was partitioned between 30 ml water and 30 ml ethyl acetate. The organic solution was washed 2×30 ml water 1×30 ml brine, dried over sodium sulfate, decanted, concentrated and purified by MPLC to give the title product. MS m/z 544 (m+1). Step 3. Preparation of (5-Methoxy-2-methyl-4-{2-[1-(4-trifluoromethyl-benzyl)-1H-indol-3-yl]-ethylsulfanyl}-phenoxy)-acetic acid (compound 54) The title compound was prepared in the manner analogous to Example 1 using 54B. 400 MHz 1H NMR (DMSO-d6) δ 13.0 (br(s), 1H), 7.60 (d, 1H, J=8.1 Hz), 7.42 (d, 1H, J=7.96 Hz), 7.31 (m, 4H), 7.04 (m, 2H), 6.96 (m, 1H), 6.53 (s, 1H), 5.43 (s, 2H), 4.70 (s, 2H), 3.72 (s, 3H), 3.03 (t, 2H, J=8.8 Hz), 2.86 (t, 2H, J=7.6 Hz), 2.04 (s, 3H). MS m/z 530 (M+1).

Workup

  1. stirringthe reaction was stirred for 1.5 h
  2. customThe DMF solution was partitioned between 30 ml water and 30 ml ethyl acetate
  3. washThe organic solution was washed 2×30 ml water 1×30 ml brine
  4. dry with materialdried over sodium sulfate
  5. customdecanted
  6. concentrationconcentrated
  7. custompurified by MPLC

Sources & evidence

ORD record
ord-6ff330207a55454e977451538ee30127
Source dataset
uspto-grants-2007_11
Patent number
USRE039916E1

Reaction notes

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