Triphenylphosphine → 4-(3-Ethoxyphenyl)-1-(2-{[6-(trifluoromethyl)pyridin-3-yl]oxy}ethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid

HRID 513190Notes

Reaction equation

HRID 513190 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:10]2[C:15]3[CH:16]=[C:17]([C:22]([O:24]C)=[O:23])[N:18]([CH2:19][CH2:20][OH:21])[C:14]=3[CH:13]=[CH:12][N:11]=2)[CH:7]=[CH:8][CH:9]=1)[CH3:2].[F:26][C:27]([F:36])([F:35])[C:28]1[N:33]=[CH:32][C:31](O)=[CH:30][CH:29]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.[OH-].[Na+]>C1COCC1>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:10]2[C:15]3[CH:16]=[C:17]([C:22]([OH:24])=[O:23])[N:18]([CH2:19][CH2:20][O:21][C:31]4[CH:32]=[N:33][C:28]([C:27]([F:36])([F:35])[F:26])=[CH:29][CH:30]=4)[C:14]=3[CH:13]=[CH:12][N:11]=2)[CH:7]=[CH:8][CH:9]=1)[CH3:2]

Participants

7

Reactant 5

HCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 27833885-Hydroxy-2-(trifluoromethyl)pyridineHCID 5363146Diisopropyl azodicarboxylateHCID 71212676Methyl 4-(3-ethoxyphenyl)-1-(2-hydroxyethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylate

Product 1

HCID 712126154-(3-Ethoxyphenyl)-1-(2-{[6-(trifluoromethyl)pyridin-3-yl]oxy}ethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acidYield 94%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

Methyl 4-(3-ethoxyphenyl)-1-(2-hydroxyethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylate (30 mg, 0.088 mmole), 6-(trifluoromethyl)pyridine-3-ol (19 mg, 0.116 mmole), and PS-triphenylphosphine resin (116 mg, 0.264 mmole) were combined in a screw cap vial. To this was added THF (1 mL) and DIAD (0.022 mL, 0.115 mmole) at RT. After stirring overnight the mixture was filtered washing with CH2Cl2 and concentrated. The residue was taken up in THF (1 mL). To this was added 2M NaOH (0.132 mL, 0.264 mmole) then the mixture was heated to 60° C. After 3 hr the mixture was cooled to RT and concentrated. The crude material was taken up in DMSO and acidified with TFA. The resulting solution was purified by preparative reversed-phase HPLC (21×100 mm Phenomenex AXIA-Gemini-NX, 15%-40% CH3CN/water containing 0.1% TFA over 18 min at 20 mL/min) to give the title compound (39 mg, 76%) as a white solid. 1H NMR (499 MHz, DMSO): δ 8.57 (d, J=6.7 Hz, 1 H); 8.46 (s, 1 H); 8.19 (s, 1H); 7.99 (d, J=8.8 Hz, 1 H); 7.63-7.55 (m, 2 H); 7.48-7.44 (m, 2 H); 7.27 (d, J=8.2 Hz, 1 H); 6.79 (d, J=8.7 Hz, 1 H); 5.18 (m, 2 H); 4.80 (m, 2 H); 4.16 (q, J=7.0 Hz, 2 H); 1.38 (t, J=6.9 Hz, 3 H). HRMS (ESI) calc (M+H)+=472.1479. found 472.1459.

Workup

  1. customcap vial
  2. filtrationwas filtered
  3. washwashing with CH2Cl2
  4. concentrationconcentrated
  5. temperatureAfter 3 hr the mixture was cooled to RT
  6. concentrationconcentrated
  7. customThe resulting solution was purified by preparative reversed-phase HPLC (21×100 mm Phenomenex AXIA-Gemini-NX, 15%-40% CH3CN/water containing 0.1% TFA over 18 min at 20 mL/min)

Sources & evidence

ORD record
ord-eba743be4ec64c04a1164d3a3742fab4
Source dataset
uspto-grants-2015_08
Patent number
US09102673B2

Reaction notes

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