Dichloromethane → 4-((8-Fluoro-6-(3-methylisoxazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methoxy)-7-(2-methoxyethoxy)quinoline

HRID 219212Notes

Reaction equation

HRID 219212 reaction equation
[F:1][C:2]1[C:3]2[N:4]([C:14]([CH2:17][O:18][C:19]3[C:28]4[C:23](=[CH:24][C:25]([OH:29])=[CH:26][CH:27]=4)[N:22]=[CH:21][CH:20]=3)=[N:15][N:16]=2)[CH:5]=[C:6]([C:8]2[O:12][N:11]=[C:10]([CH3:13])[CH:9]=2)[CH:7]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[CH3:49][O:50][CH2:51][CH2:52]O.C(Cl)Cl.CCOC(/N=N/C(OCC)=O)=O>>[F:1][C:2]1[C:3]2[N:4]([C:14]([CH2:17][O:18][C:19]3[C:28]4[C:23](=[CH:24][C:25]([O:29][CH2:52][CH2:51][O:50][CH3:49])=[CH:26][CH:27]=4)[N:22]=[CH:21][CH:20]=3)=[N:15][N:16]=2)[CH:5]=[C:6]([C:8]2[O:12][N:11]=[C:10]([CH3:13])[CH:9]=2)[CH:7]=1

Participants

6

Reactant 5

HCID 6344DichloromethaneHCID 80192-MethoxyethanolHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 1359874714-((8-Fluoro-6-(3-methylisoxazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methoxy)quinolin-7-ol

Product 1

HCID 441812514-((8-Fluoro-6-(3-methylisoxazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methoxy)-7-(2-methoxyethoxy)quinolineYield 55.6%

Conditions

Temperature
0 °C

Procedure

4-((8-fluoro-6-(3-methylisoxazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methoxy)quinolin-7-ol (0.110 g, 0.28 mmol), PPh3 (polymer supported: 2.3 mmol/g) (1.2 g, 2.8 mmol) and 2-methoxyethanol (0.11 ml, 1.3 mmol) were combined in DCM (11 ml, 0.28 mmol). The mixture was cooled to 0° C., and DEAD (0.089 ml, 0.56 mmol) was added dropwise. The reaction was removed from the ice bath, and stirred at RT for 1 h. The material was diluted with DCM, and the PS—PPh3 was filtered off and washed thoroughly with DCM. The filtrate was concentrated in vacuo. The crude material was dissolved in minimal DCM and purified via MPLC (eluting with 0-100% 90:10:1 DCM:MeOH:NH4OH in DCM) to yield 4-((8-fluoro-6-(3-methylisoxazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methoxy)-7-(2-methoxyethoxy)quinoline (0.070 g, 55% yield) as a white solid. MS (ESI pos. ion) m/z: 450.0 (M+H). Calc'd Exact Mass for C23H20FN5O4: 449.44

Workup

  1. customThe reaction was removed from the ice bath
  2. additionThe material was diluted with DCM
  3. filtrationthe PS—PPh3 was filtered off
  4. washwashed thoroughly with DCM
  5. concentrationThe filtrate was concentrated in vacuo
  6. dissolutionThe crude material was dissolved in minimal DCM
  7. custompurified via MPLC (eluting with 0-100% 90:10:1 DCM:MeOH:NH4OH in DCM)

Sources & evidence

ORD record
ord-b1ffa914ee1e4f7ea20e5f99223fae6b
Source dataset
uspto-grants-2012_06
Patent number
US08198448B2

Reaction notes

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