HCID 90431675, compound → HCID 90386199, compound

HRID 2170184Notes

Reaction equation

HRID 2170184 reaction equation
[C:1]1([C:7]2[CH:8]=[CH:9][N:10]3[C:15]=2[C:14]([NH:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=2)=[N:13][C:12]([C:24]2[CH:25]=[C:26](/[CH:30]=[CH:31]/[S:32]([NH:35]C(=O)OC(C)(C)C)(=[O:34])=[O:33])[CH:27]=[N:28][CH:29]=2)=[N:11]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>CCOC(C)=O.[Pd]>[C:1]1([C:7]2[CH:8]=[CH:9][N:10]3[C:15]=2[C:14]([NH:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=2)=[N:13][C:12]([C:24]2[CH:25]=[C:26]([CH2:30][CH2:31][S:32]([NH2:35])(=[O:33])=[O:34])[CH:27]=[N:28][CH:29]=2)=[N:11]3)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

4

Reactant 1

HCID 90431675HCID 90431675, compound

Product 1

HCID 90386199HCID 90386199, compoundYield 18.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of (E)-tert-butyl (2-(5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridin-3-yl)vinyl)sulfonylcarbamate (100 mg, 0.171 mmol) in EtOAc (20 mL) was added 10% Pd/C (36.5 mg, 0.343 mmol) and the reaction mixture stirred for 12 h at RT under the H2 atmosphere using a bladder. The reaction mixture was filtered through a pad of CELITE® and the filtrate was treated with TFA (1 mL) then stirred at RT for 4 h. The volatile components were removed under reduced pressure. The resulting residue was dissolved in DCM (100 mL) and washed with 10% NaHCO3 (50 mL). The organic layer was separated, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC (Condition B-95 as described in general methods) to give 2-(5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridin-3-yl)ethanesulfonamide (15.0 mg, 18.0%). LCMS Condition B-83: retention time 0.995 min, [M+1]=486.0, Purity: 96.17%. 1H NMR (400 MHz, CD3OD) δ ppm 3.24-3.30 (m, 2H), 3.42-3.52 (m, 2H), 4.90-4.93 (m, 2H), 6.77 (d, J=2.7 Hz, 1H), 7.30 (dd, J=7.0 Hz, J=5.3 Hz, 1H), 7.43-7.48 (m, 2H), 7.49-7.56 (m, 2H), 7.58-7.63 (m, 2H), 7.76 (d, J=2.7 Hz, 1H), 7.80 (td, J=7.7 Hz, J=1.8 Hz, 1H), 8.46 (d, J=4.2 Hz, 1H), 8.50-8.56 (m, 2H), 9.25 (d, J=2.0 Hz, 1H).

Workup

  1. filtrationThe reaction mixture was filtered through a pad of CELITE®
  2. additionthe filtrate was treated with TFA (1 mL)
  3. stirringthen stirred at RT for 4 h
  4. customThe volatile components were removed under reduced pressure
  5. dissolutionThe resulting residue was dissolved in DCM (100 mL)
  6. washwashed with 10% NaHCO3 (50 mL)
  7. customThe organic layer was separated
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by preparative HPLC (Condition B-95 as described in general methods)

Sources & evidence

ORD record
ord-a954de31c03346548053e22e5c76bf04
Source dataset
uspto-grants-2015_06
Patent number
US09050345B2

Reaction notes

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