Formamidine acetate → Benzyl 3-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)azetidine-1-carboxylate

HRID 1972946Notes

Reaction equation

HRID 1972946 reaction equation
[NH2:1][N:2]1[C:6]([C:7]#[N:8])=[CH:5][CH:4]=[C:3]1[CH:9]1[CH2:12][N:11]([C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:14])[CH2:10]1.C(O)(=O)C.[CH:27](N)=[NH:28]>C(O)CCC>[NH2:8][C:7]1[C:6]2=[CH:5][CH:4]=[C:3]([CH:9]3[CH2:10][N:11]([C:13]([O:15][CH2:16][C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)=[O:14])[CH2:12]3)[N:2]2[N:1]=[CH:27][N:28]=1

Participants

4

Reactant 2

HCID 160693Formamidine acetateHCID 58529445benzyl 3-(1-amino-5-cyano-1H-pyrrol-2-yl)azetidine-1-carboxylate

Product 1

HCID 58529502Benzyl 3-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)azetidine-1-carboxylateYield 40%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A solution of benzyl 3-(1-amino-5-cyano-1H-pyrrol-2-yl)azetidine-1-carboxylate (575 mg, 1.94 mmoL) and formamidine acetate (2.02 g, 19.4 mmol) in 1-butanol (8 mL) was stirred at 120° C. for 4 hours. The mixture was then cooled to rt and was partitioned between EtOAc (25 mL) and H2O (25 mL). The layers were separated and the aqueous layer was further extracted with EtOAc (2×25 mL). The combined organic layers were washed with brine, dried (Na2SO4) and concentrated. The crude material was purified by ISCO® chromatography using 3:1 ethyl acetate/hexanes to obtain 250 mg (40%) of the desired product. ES-MS m/z 324.34 [M+H]+, HPLC RT (min) 2.30.

Workup

  1. customwas partitioned between EtOAc (25 mL) and H2O (25 mL)
  2. customThe layers were separated
  3. extractionthe aqueous layer was further extracted with EtOAc (2×25 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude material was purified by ISCO® chromatography

Sources & evidence

ORD record
ord-1a857b3795434ff98ec34a023cf5bada
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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