Aniline → HCID 89783279, compound

HRID 1055921Notes

Reaction equation

HRID 1055921 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]([OH:23])=O)[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][C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1>CN(C=O)C.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][C:56]3[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=3)=[O:23])[CH:17]=[CH:16]4)[NH:10][C:6]=2[CH2:5][CH2:4][NH:3]1

Participants

7

Reactant 4

HCID 6115AnilineHCID 8471TriethylamineHCID 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 89783279HCID 89783279, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 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; 80 mg, 0.26 mmol) was dissolved in DMF (2.5 mL), HATU (119 mg, 0.31 mmol), Et3N (0.04 mL, 0.31 mmol), and aniline (0.05 mL, 0.52 mmol) were added, and the resulting mixture was stirred at RT for 20 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 to in vacuo. DCM was added to the crude material and a precipitate was formed, which contained both the desired product and impurities. Most of the impurities crystallized from hot DCM, and were removed by filtration. The mother liquor was concentrated and the material (desired product and ca. 10% impurity) was suspended in EtOAc. The desired product was recrystallized from hot EtOAc and was isolated by filtration affording 8-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)-N-phenylquinoline-2-carboxamide (12.9 mg, 0.034 mmol, 13.0% yield) as an amorphous tan solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 12.04 (br. s., 1H), 10.55 (s, 1H), 8.68 (d, J=8.4 Hz, 1H), 8.25 (d, J=8.4 Hz, 1H), 8.11 (d, J=7.2 Hz, 1H), 7.99 (d, J=7.6 Hz, 1H), 7.93 (d, J=8.0 Hz, 2H), 7.72-7.81 (m, 1H), 7.44 (t, J=7.7 Hz, 2H), 7.13-7.22 (m, 1H), 7.07 (d, J=10.8 Hz, 2H), 3.44-3.53 (m, 2H), 2.95 (t, J=6.7 Hz, 2H). m/z (ESI, +ve ion) 383.0 (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 to in vacuo
  7. additionDCM was added to the crude material
  8. customa precipitate was formed

Sources & evidence

ORD record
ord-2d109ed9f7834eef8077d0572bf52f55
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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