Ethyl Acetate → HCID 71133987, compound

HRID 1972970Notes

Reaction equation

HRID 1972970 reaction equation
[CH3:1][C:2]([O:5][C:6]([N:8]([CH2:10][C:11]([OH:13])=O)[CH3:9])=[O:7])([CH3:4])[CH3:3].C(N(C(C)C)CC)(C)C.[NH2:23][C:24]1[N:25]([CH2:49][C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)[N:26]=[C:27]2[C:32]=1[CH:31]=[CH:30][C:29]([C:33]1[CH:34]=[C:35]([CH:43]3[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]3)[N:36]3[C:41]=1[C:40]([NH2:42])=[N:39][CH:38]=[N:37]3)=[CH:28]2.CCOC(C)=O>C1COCC1.ClCCCl>[C:2]([O:5][C:6](=[O:7])[N:8]([CH2:10][C:11]([N:46]1[CH2:47][CH2:48][CH:43]([C:35]2[N:36]3[C:41]([C:40]([NH2:42])=[N:39][CH:38]=[N:37]3)=[C:33]([C:29]3[CH:30]=[CH:31][C:32]4[C:27]([CH:28]=3)=[N:26][N:25]([CH2:49][C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)[C:24]=4[NH2:23])[CH:34]=2)[CH2:44][CH2:45]1)=[O:13])[CH3:9])([CH3:1])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 83692Glycine, N-[(1,1-dimethylethoxy)carbonyl]-N-methyl-HCID 58529681HCID 58529681, compound

Product 1

HCID 71133987HCID 71133987, compoundYield 37.2%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

To a stirred solution of N-t-BOC-sarcosine (44.0 mg, 0.233 mmol, 1.2 eq), ByPOP (120 mg, 0.27 mmol, 1.4 eq), and diisopropylethylamine (0.10 mL, 0.58 mmol, 3.0 eq) in anhydrous THF (1.9 mL) and DCE (1.0 mL) was added 5-(3-amino-2-benzyl-2H-indazol-6-yl)-7-piperidin-4-yl-pyrrolo[2,1-f][1,2,4]triazin-4-ylamine (85 mg, 0.194 mmol). The reaction mixture was stirred at 40° C. under N2 for 18 h and cooled to rt. The mixture was cooled and poured into EtOAc. The organic phase was washed with water and brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was dissolved in anhydrous THF (2.0 mL), and 1.0 M sodium methoxide in MeOH (0.5 mL) was added. The reaction mixture was stirred at it for 18 h and poured into EtOAc. The organic layer was washed with water and brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified using an ISCO® instrument (gradient 0 to 25% MeOH/EtOAc) and the product containing fractions were concentrated. Trituration with DCM-hexane afforded 43.9 mg (37.2%) of the title compound as pink solid. 1H NMR (300 MHz, DMSO-d6) δ 7.89 (s, 1H), 7.71 (d, 1H), 7.34 to 7.29 (m, 2H), 7.27 to 7.14 (m, 3H), 7.15 (t, 1H), 6.73 (t, 1H), 6.56 (s, 0.5H), 6.48 (s, 0.5H), 6.37 (s, 2H), 5.38 (s, 2H), 4.50 to 4.45 (m, 1H), 4.13 to 3.83 (m, 3H), 3.44 to 3.35 (m, 1H), 3.16 (t, 1H), 2.78 to 2.70 (m, 4H), 2.07 to 2.04 (m, 2H), 1.66 to 1.51 (m, 2H), 1.35 (d, 9H); ES-MS m/z 610.0 [M+H]+, RT (min) 2.55.

Workup

  1. temperaturecooled to rt
  2. temperatureThe mixture was cooled
  3. washThe organic phase was washed with water and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was dissolved in anhydrous THF (2.0 mL)
  8. addition1.0 M sodium methoxide in MeOH (0.5 mL) was added
  9. stirringThe reaction mixture was stirred at it for 18 h
  10. additionpoured into EtOAc
  11. washThe organic layer was washed with water and brine
  12. dry with materialdried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customThe crude product was purified
  16. additionthe product containing fractions
  17. concentrationwere concentrated

Sources & evidence

ORD record
ord-1fe230b9129949aaa16f5713257b367c
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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