Dimethylformamide → HCID 66711158, compound

HRID 1262092Notes

Reaction equation

HRID 1262092 reaction equation
[CH3:1][O:2][C:3]1[N:4]=[N:5][C:6]([O:19][CH3:20])=[CH:7][C:8]=1[C:9]1[N:17]2[C:12]([CH:13]=[N:14][C:15](O)=[N:16]2)=[CH:11][CH:10]=1.C1C=CC(N(S(C(F)(F)F)(=O)=O)S(C(F)(F)F)(=O)=O)=CC=1.C(N(CC)C(C)C)(C)C.CN(C)C=O.[NH2:56][C:57]1[CH:62]=[CH:61][C:60]([CH:63]2[CH2:68][CH2:67][N:66]([CH2:69][C:70]([NH2:72])=[O:71])[CH2:65][CH2:64]2)=[CH:59][CH:58]=1>>[CH3:1][O:2][C:3]1[N:4]=[N:5][C:6]([O:19][CH3:20])=[CH:7][C:8]=1[C:9]1[N:17]2[C:12]([CH:13]=[N:14][C:15]([NH:56][C:57]3[CH:62]=[CH:61][C:60]([CH:63]4[CH2:64][CH2:65][N:66]([CH2:69][C:70]([NH2:72])=[O:71])[CH2:67][CH2:68]4)=[CH:59][CH:58]=3)=[N:16]2)=[CH:11][CH:10]=1

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 142176Phenyl triflimideHCID 574161072-[4-(4-Aminophenyl)piperidin-1-yl]acetamideHCID 178487405HCID 178487405, compound

Product 1

HCID 66711158HCID 66711158, compoundYield 15.4%

Procedure

7-(3,6-Dimethoxy-pyridazin-4-yl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (70 mg, 0.2 mmol), N-Phenylbis(trifluoromethanesulphonimide) (95.1 mg, 0.266 mmol), N,N-Diisopropylethylamine (0.126 mL, 0.726 mmol), and N,N-Dimethylformamide (2 mL, 30 mmol) and stir at room temperature for half an hour. Add 2-[4-(4-Amino-phenyl)-piperidin-1-yl]-acetamide (90.3 mg, 0.387 mmol) and stir at 60° C. overnight. An LCMS showed product. The reaction was concentrated, DMSO added, filtered and placed onto the Gilson for purification. The most pure fractions were collected, free based with saturated sodium bicarbonate, extracted with DCM, filtered and concentrated to give 2-(4-{4-[7-(3,6-Dimethoxy-pyridazin-4-yl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidin-1-yl)-acetamide as a yellow solid (15 mg, 10%). MP 249-251° C. LCMS (E/I+) 489 (M+H). NMR 1H (DMSO-d6)-9.56 (s, 1H), 9.1 (s, 1H), 8.27 (s, 1H), 7.60 (d, 2H, J=8.30 Hz), 7.40 (d, 2H, J=4.82 Hz), 7.21 (bs, 1H), 7.18 (d, 1H, J=8.42 Hz), 7.13 (bs, 1H), 6.97 (d, 1H, J=4.87 Hz), 4.06 (s, 3H), 4.04 (s, 3H), 2.87-2.96 (m, 4H), 2.40-2.48 (m, 1H), 2.14-2.25 (m, 2H), 1.70-1.78 (m, 4H).

Workup

  1. concentrationThe reaction was concentrated
  2. additionDMSO added
  3. filtrationfiltered
  4. customplaced onto the Gilson for purification
  5. customThe most pure fractions were collected
  6. extractionextracted with DCM
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-213898938b424dd8ab011b9492277a2f
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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