Aniline → 2-(2-(phenylamino)quinolin-8-yl)oxazolo[4,5-c]pyridin-4(5H)-one

HRID 1056001Notes

Reaction equation

HRID 1056001 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.Cl[C:12]1[CH:21]=[CH:20][C:19]2[C:14](=[C:15]([C:22]3[O:23][C:24]4[CH:29]=[CH:28][NH:27][C:26](=[O:30])[C:25]=4[N:31]=3)[CH:16]=[CH:17][CH:18]=2)[N:13]=1.[NH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>O1CCOCC1.CCOC(C)=O>[C:33]1([NH:32][C:12]2[CH:21]=[CH:20][C:19]3[C:14](=[C:15]([C:22]4[O:23][C:24]5[CH:29]=[CH:28][NH:27][C:26](=[O:30])[C:25]=5[N:31]=4)[CH:16]=[CH:17][CH:18]=3)[N:13]=2)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

6

Reactant 3

HCID 6115AnilineHCID 2733832Lithium HexamethyldisilazideHCID 897823932-(2-chloroquinolin-8-yl)oxazolo[4,5-c]pyridin-4(5H)-one

Product 1

HCID 897821042-(2-(phenylamino)quinolin-8-yl)oxazolo[4,5-c]pyridin-4(5H)-oneYield 14%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

LHMDS (1.0M in THF; 2015 μl, 2.015 mmol) was added to a solution of 2-(2-chloroquinolin-8-yl)oxazolo[4,5-c]pyridin-4(5H)-one (Example 181; 120 mg, 0.403 mmol) and aniline (184 μl, 2.015 mmol) in dioxane (4031 μl) at RT; and the resulting mixture was stirred at RT for 30 min. The mixture was diluted with EtOAc (150 ml), added to a separatory funnel, and washed with saturated aq. NH4Cl (2×100 ml) before the organic layer was separated, dried over Na2SO4, and concentrated. Purification by silica gel (100% DCM to 5% MeOH/DCM) provided 2-(2-(phenylamino)quinolin-8-yl)oxazolo[4,5-c]pyridin-4(5H)-one (14% yield) as a dark orange solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 6.87-6.94 (m, 2H) 7.16 (d, J=9.00 Hz, 1H) 7.27 (t, J=7.82 Hz, 2H) 7.45 (t, J=7.63 Hz, 1H) 7.55 (t, J=6.55 Hz, 1H) 7.98 (d, J=6.85 Hz, 1H) 8.10 (d, J=7.83 Hz, 2H) 8.15-8.20 (m, 2H) 9.69 (s, 1H) 11.87 (br. s., 1H). MS (ESI, pos. ion) m/z: 355.1 (M+1).

Workup

  1. additionadded to a separatory funnel
  2. washwashed with saturated aq. NH4Cl (2×100 ml) before the organic layer
  3. customwas separated
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customPurification by silica gel (100% DCM to 5% MeOH/DCM)

Sources & evidence

ORD record
ord-84f5b1fb20ff48e79a0f914afb78cec3
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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