Methanol → HCID 89784319, compound

HRID 1055967Notes

Reaction equation

HRID 1055967 reaction equation
[CH3:1][C:2]1[C:3]([NH:22][CH:23]2[CH2:26][N:25](C(OC(C)(C)C)=O)[CH2:24]2)=[N:4][C:5]2[C:10]([N:11]=1)=[CH:9][CH:8]=[CH:7][C:6]=2[C:12]1[NH:20][C:19]2[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=2[CH:13]=1.[C:34]([OH:40])([C:36]([F:39])([F:38])[F:37])=[O:35].CO>C(Cl)Cl>[F:37][C:36]([F:39])([F:38])[C:34]([OH:40])=[O:35].[NH:25]1[CH2:24][CH:23]([NH:22][C:3]2[C:2]([CH3:1])=[N:11][C:10]3[C:5]([N:4]=2)=[C:6]([C:12]2[NH:20][C:19]4[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=4[CH:13]=2)[CH:7]=[CH:8][CH:9]=3)[CH2:26]1

Participants

5

Reactant 3

HCID 887MethanolHCID 6422Trifluoroacetic acidHCID 89784076HCID 89784076, compound

Product 1

HCID 89784319HCID 89784319, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl 3-((3-methyl-8-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)quinoxalin-2-yl)amino)azetidine-1-carboxylate (98.0 mg, 0.218 mmol) and TFA (1.0 mL, 12.98 mmol) in DCM (2.0 mL) was stirred at 25° C. for 1 h. MeOH (2 mL) was added, and the mixture was concentrated in vacuo. The residue was partitioned between 5% MeOH/DCM (80 mL) and saturated aq. NaHCO3 (50 mL). The aq. layer was separated and concentrated in vacuo. Sonication of the residue with 5% MeOH/DCM (80 mL, then 2×40 mL) and concentration of the combined organic layers provided a yellow-orange oil. This oil was triturated with Et2O, the supernatant was drawn off, and the precipitated residue was taken up in 5% MeOH/DCM, filtered, and dried in vacuo to provide a yellow foam. Purification of this foam by reversed-phase HPLC (Phenomenex Gemini C18 column (150×30 mm, 10 μm), 35 mL/min, 5-100% ACN/H2O+0.1% TFA) furnished 2-(3-(azetidin-3-ylamino)-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one 2,2,2-trifluoroacetate (41.0 mg, 0.089 mmol, 41% yield) as a red-brown solid: 1H NMR (400 MHz, MeOH-d4) δ ppm 11.47 (1H, br. s.), 7.78 (1H, d, J=7.2 Hz), 7.69 (1H, d, J=8.0 Hz), 7.45 (1H, t, J=8.0 Hz), 7.34 (1H, d, J=2.0 Hz), 5.21 (1H, quin, J=7.5 Hz), 4.43-4.51 (2H, m), 4.18-4.28 (2H, m), 3.63 (2H, t, J=7.0 Hz), 3.01 (2H, t, J=7.0 Hz), 2.64 (3H, s). 19F NMR (376 MHz, MeOH-d4) δ ppm −77.58 (3F, s). m/z (ESI, +ve) 349.1 (M+H)+.

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. customThe residue was partitioned between 5% MeOH/DCM (80 mL) and saturated aq. NaHCO3 (50 mL)
  3. customThe aq. layer was separated
  4. concentrationconcentrated in vacuo
  5. customSonication of the residue with 5% MeOH/DCM (80 mL
  6. custom2×40 mL) and concentration of the combined organic layers provided a yellow-orange oil
  7. customThis oil was triturated with Et2O
  8. filtrationfiltered
  9. customdried in vacuo
  10. customto provide a yellow foam
  11. customPurification of this foam by reversed-phase HPLC (Phenomenex Gemini C18 column (150×30 mm, 10 μm), 35 mL/min, 5-100% ACN/H2O+0.1% TFA)

Sources & evidence

ORD record
ord-688176c2650646608baa9154c67c02f9
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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