Triethylamine → HCID 89783970, compound

HRID 1055922Notes

Reaction equation

HRID 1055922 reaction equation
[O:1]=[C:2]1[C:7]2[CH:8]=[C:9]([C:11]3[CH:12]=[CH:13][CH:14]=[C:15]4[C:20]=3[N:19]=[C:18]([C:21](O)=[O:22])[CH:17]=[CH:16]4)[NH:10][C:6]=2[CH2:5][CH2:4][NH:3]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC.[NH2:55][CH:56]1[CH2:61][CH2:60][O:59][CH2:58][CH2:57]1>CN(C=O)C.C(Cl)Cl.CCOC(C)=O>[O:1]=[C:2]1[C:7]2[CH:8]=[C:9]([C:11]3[CH:12]=[CH:13][CH:14]=[C:15]4[C:20]=3[N:19]=[C:18]([C:21]([NH:55][CH:56]3[CH2:61][CH2:60][O:59][CH2:58][CH2:57]3)=[O:22])[CH:17]=[CH:16]4)[NH:10][C:6]=2[CH2:5][CH2:4][NH:3]1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 4192234-AminotetrahydropyranHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 89783435HCID 89783435, compound

Product 1

HCID 89783970HCID 89783970, compoundYield 32%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

8-(4-Oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)quinoline-2-carboxylic acid (Example 94e; 77 mg, 0.25 mmol) was dissolved in DMF (1.5 mL), HATU (114 mg, 0.30 mmol), Et3N (0.04 mL, 0.30 mmol), and 4-aminotetrahydropyran (Combi-Blocks Inc., San Diego, Calif.; 0.05 mL, 0.50 mmol) were added, and the resulting mixture was stirred at RT for 25 min. The mixture was then treated with EtOAc and washed with water. The organic layer was separated, and the aq. layer was extracted with EtOAc (2×). The combined organic layers were then dried over MgSO4, filtered, and concentrated. The residue was treated with DCM, and a precipitate formed. The DCM was heated, but the precipitate did not dissolve. The suspension was held at RT for 1 h, after which the solid was removed by filtration to give 8-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)-N-(tetrahydro-2H-pyran-4-yl)quinoline-2-carboxamide (31.2 mg, 0.08 mmol, 32% yield) as a bright yellow amorphous solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 12.00 (br. s., 1H), 8.55-8.67 (m, 2H), 8.08-8.16 (m, 2H), 7.93 (d, J=7.8 Hz, 1H), 7.68-7.77 (m, 1H), 6.94-7.05 (m, 2H), 4.00-4.15 (m, 1H), 3.90 (d, J=11.7 Hz, 2H), 3.42-3.52 (m, 4H), 2.91 (t, J=6.7 Hz, 2H), 1.92 (d, J=12.1 Hz, 2H), 1.59-1.74 (m, 2H). m/z (ESI, +ve ion) 391.1 (M+H)+.

Workup

  1. washwashed with water
  2. customThe organic layer was separated
  3. extractionthe aq. layer was extracted with EtOAc (2×)
  4. dry with materialThe combined organic layers were then dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. additionThe residue was treated with DCM
  8. customa precipitate formed
  9. dissolutionthe precipitate did not dissolve
  10. waitThe suspension was held at RT for 1 h
  11. customafter which the solid was removed by filtration

Sources & evidence

ORD record
ord-bd750962948046d6b0a21f320f73f2c1
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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