Methanol → 1-{4-Aminopyrrolo[2,1-f][1,2,4]triazin-6-yl}ethan-1-ol

HRID 73668Notes

Reaction equation

HRID 73668 reaction equation
C[Mg]Br.[NH2:4][C:5]1[C:10]2=[CH:11][C:12]([CH:14]=[O:15])=[CH:13][N:9]2[N:8]=[CH:7][N:6]=1.[CH3:16]O.[NH4+].[Cl-]>C(OCC)C.C1COCC1.CCOC(C)=O>[NH2:4][C:5]1[C:10]2=[CH:11][C:12]([CH:14]([OH:15])[CH3:16])=[CH:13][N:9]2[N:8]=[CH:7][N:6]=1

Participants

8

Reactant 4

HCID 887MethanolHCID 25517Ammonium ChlorideHCID 579553014-Aminopyrrolo[2,1-f][1,2,4]triazine-6-carbaldehydeHCID 178418573HCID 178418573, compound

Product 1

HCID 552977291-{4-Aminopyrrolo[2,1-f][1,2,4]triazin-6-yl}ethan-1-olYield 56%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of THF (100 mL) was added 3.0 M methylmagnesium bromide in diethyl ether (14.0 mL, 41.9, mmol) cooled in an ice bath. Then 4-aminopyrrolo[2,1-f][1,2,4]triazine-6-carbaldehyde (0.68 g, 4.19 mmol) was added as a solution in THF (200 mL) via an addition funnel. The reaction was allowed to slowly warm to rt over the following 17 h. The reaction was carefully treated with MeOH (10 mL) followed by aq saturated NH4Cl (50 mL) and EtOAc (50 mL). The solution was transferred to a separatory funnel and the organic layer was isolated while the aqueous layer was back extracted with EtOAc (4×20 mL). The combined organic layers were collected, dried (MgSO4), filtered, and concentrated to dryness. The crude material was then purified by flash chromatography (85:15 v/v CH2Cl2-MeOH). The purified fractions were concentrated in vacuo and then dried under vacuum to afford 422 mg of the above compound (2.37 mmol, yield 56%). 1H-NMR (DMSO-d6) δ 7.72 (s, 1H), 7.59 (br s, 2H), 7.45 (dd, J=0.5 Hz, 1.7 Hz, 1H), 6.76 (dd, J=0.5 Hz, 1.7 Hz, 1H), 5.03 (d, J=4.7 Hz, 1H), 4.79 (m, 1H), 1.38 (d, J=6.5 Hz, 3H); MS [M+H]+=179.3; LCMS RT=1.04 min.

Workup

  1. temperaturecooled in an ice bath
  2. customThe solution was transferred to a separatory funnel
  3. customthe organic layer was isolated while the aqueous layer
  4. extractionwas back extracted with EtOAc (4×20 mL)
  5. customThe combined organic layers were collected
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. customThe crude material was then purified by flash chromatography (85:15 v/v CH2Cl2-MeOH)
  10. concentrationThe purified fractions were concentrated in vacuo
  11. customdried under vacuum

Sources & evidence

ORD record
ord-5bd50f5bf76a4994a3232d77fe0e59f5
Source dataset
uspto-grants-2014_09
Patent number
US08829185B2

Reaction notes

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