Sodium hydride → (6-Methoxy-2-oxetan-3-yl-2,3-dihydro-1H-isoindol-5-yl)-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-amine

HRID 1262134Notes

Reaction equation

HRID 1262134 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[N:17]2[C:12]([CH:13]=[N:14][C:15](O)=[N:16]2)=[CH:11][CH:10]=1.[H-].[Na+].C1C=CC(N(S(C(F)(F)F)(=O)=O)S(C(F)(F)F)(=O)=O)=CC=1.[O-]S(C(F)(F)F)(=O)=O.[CH3:50][O:51][C:52]1[CH:60]=[C:59]2[C:55]([CH2:56][N:57]([CH:61]3[CH2:64][O:63][CH2:62]3)[CH2:58]2)=[CH:54][C:53]=1[NH2:65]>CN(C)C=O>[CH3:50][O:51][C:52]1[CH:60]=[C:59]2[C:55]([CH2:56][N:57]([CH:61]3[CH2:62][O:63][CH2:64]3)[CH2:58]2)=[CH:54][C:53]=1[NH:65][C:15]1[N:14]=[CH:13][C:12]2=[CH:11][CH:10]=[C:9]([C:4]3[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=3[O:2][CH3:1])[N:17]2[N:16]=1

Participants

7

Reactant 5

HCID 24758Sodium hydrideHCID 142176Phenyl triflimideHCID 2758875TrifluoromethanesulfonateHCID 574160836-Methoxy-2-(oxetan-3-yl)-2,3-dihydro-1H-isoindol-5-amineHCID 1784892767-(2-Methoxyphenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol

Product 1

HCID 66711333(6-Methoxy-2-oxetan-3-yl-2,3-dihydro-1H-isoindol-5-yl)-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-amineYield 12%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

7-(2-Methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (50.00 mg, 0.207) was dissolved in N,N-Dimethylformamide (4.0 mL) at 0° C. and sodium hydride (60% dispersion in mineral oil; 10.4 mg, 0.259 mmol) was added and the reaction was let to stir for 30 minutes. Then, N-phenylbis(trifluoromethanesulphonimide) (81.4 mg, 0.228 mmol) was added and the reaction was allowed to warm to room temperature. After 100% conversion to the triflate, 6-methoxy-2-oxetan-3-yl-2,3-dihydro-1H-isoindol-5-ylamine (57.1 mg, 0.259 mmol 1) was added the reaction was allowed to stir at room temperature. The reaction mixture was partitioned between dichloromethane and saturated aqueous Na2CO3. The aqueous layer was extracted with dichloromethane, the combined organics were dried over sodium sulfate and filtered. The solvent was evaporated under reduced pressure and the product was isolated by preparative reverse phase hplc (Gilson) as a brown foam (11 mg, 12%). 1H-NMR (CDCl3) δ 8.70 (s, 1H), 8.27 (s, 1H), 7.96 (d, J=7.2 Hz, 1H), 7.51 (br s, 1H), 7.42 (m, 1H), 7.08 (m, 2H), 7.02 (d, J=4.6 Hz, 1H), 6.84 (d, J=4.6 Hz, 1H) 6.74 (br s, 1H), 4.78 (m, 4H), 4.09 (m, 1H), 3.95 (br s, 2H), 3.89 (s, 3H), 3.85 (br s, 2H), 3.83 (s, 3H); LC/MS (ESI+): 444.0 (M+H).

Workup

  1. stirringto stir at room temperature
  2. customThe reaction mixture was partitioned between dichloromethane and saturated aqueous Na2CO3
  3. extractionThe aqueous layer was extracted with dichloromethane
  4. dry with materialthe combined organics were dried over sodium sulfate
  5. filtrationfiltered
  6. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-6d5b31652b704e95ae21f12ce5bee1ae
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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