N-bromobutanimide → HCID 21081533, compound

HRID 2117131Notes

Reaction equation

HRID 2117131 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][N:5]2[C:10]=1[C:9]([S:11][CH3:12])=[N:8][CH:7]=[N:6]2.C1C(=O)N(Br)C(=O)C1.[OH:21][CH:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1.CCN(C(C)C)C(C)C>C(Cl)(Cl)(Cl)Cl>[CH3:12][S:11][C:9]1[C:10]2=[C:2]([CH2:1][N:25]3[CH2:26][CH2:27][CH:22]([OH:21])[CH2:23][CH2:24]3)[CH:3]=[CH:4][N:5]2[N:6]=[CH:7][N:8]=1

Participants

6

Reactant 4

HCID 67184N-bromobutanimideHCID 79341Piperidin-4-olHCID 81531DiisopropylethylamineHCID 210315125-Methyl-4-(methylsulfanyl)pyrrolo[2,1-f][1,2,4]triazine

Product 1

HCID 21081533HCID 21081533, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 5943Carbon TetrachlorideSolvent

Procedure

A solution of 5-methyl-4-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazine (200 mg, 1.12 mmol), NBS (218 mg, 1.23 mmol), and AKIN (spatula tip) in carbon tetrachloride (4 mL) was heated at 80° C. for 1 h. After cooling to rt, the solution was filtered to remove succinimide. To the filtrate was added 4-hydroxypiperidine (126 mg, 1.34 mmol, Aldrich) and DIPEA (214 μL, 1.23 mmol). The reaction was stirred at rt overnight and was then concentrated in vacuo. The residue was suspended in methanol and filtered. The filtrate was concentrated and the crude product was purified by flash chromatography on silica gel (20% MeOH/EtOAc) to give the title compound (229 mg, 74%) as a colorless solid. 1 H NMR (DMSO-d6) δ 8.25 (s, 1H), 7.88 (d, 1H, J=2 Hz), 6.81 (d, 1H, J=2 Hz), 4.54 (br s, 1H), 3.76 (s, 2H), 3.48-3.44 (m, 1H), 2.75-2.71 (m, 2H), 2.62 (s, 3H), 2.10-2.08 (m, 2H), 1.70-1.68 (m, 2H), 1.38-1.36 (m, 2H); MS(ESI+) m/z 279.3 (M+H)+.

Workup

  1. filtrationthe solution was filtered
  2. customto remove succinimide
  3. concentrationwas then concentrated in vacuo
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated
  6. customthe crude product was purified by flash chromatography on silica gel (20% MeOH/EtOAc)

Sources & evidence

ORD record
ord-085cfdf915bb48a1a519f1c377d2031b
Source dataset
uspto-grants-2008_10
Patent number
US07439246B2

Reaction notes

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