Trifluoroacetic acid → 2-methoxy-5-(5-phenyl-4-(5H-pyrrolo[3,4-b]pyridin-6(7H)-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridine-3-sulfonamide

HRID 2170191Notes

Reaction equation

HRID 2170191 reaction equation
C([NH:5][S:6]([C:9]1[C:10]([O:39][CH3:40])=[N:11][CH:12]=[C:13]([C:15]2[N:20]=[C:19]([N:21]3[CH2:29][C:28]4[C:23](=[N:24][CH:25]=[CH:26][CH:27]=4)[CH2:22]3)[C:18]3=[C:30]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[CH:31]=[CH:32][N:17]3[N:16]=2)[CH:14]=1)(=[O:8])=[O:7])(C)(C)C.C(O)(C(F)(F)F)=O>C([O-])(O)=O.[Na+]>[CH3:40][O:39][C:10]1[C:9]([S:6]([NH2:5])(=[O:8])=[O:7])=[CH:14][C:13]([C:15]2[N:20]=[C:19]([N:21]3[CH2:29][C:28]4[C:23](=[N:24][CH:25]=[CH:26][CH:27]=4)[CH2:22]3)[C:18]3=[C:30]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[CH:31]=[CH:32][N:17]3[N:16]=2)=[CH:12][N:11]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90386064N-(tert-butyl)-2-methoxy-5-(5-phenyl-4-(5H-pyrrolo[3,4-b]pyridin-6(7H)-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridine-3-sulfonamide

Product 1

HCID 903864742-methoxy-5-(5-phenyl-4-(5H-pyrrolo[3,4-b]pyridin-6(7H)-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridine-3-sulfonamideYield 19.8%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
70 °C

Procedure

N-(tert-Butyl)-2-methoxy-5-(5-phenyl-4-(5H-pyrrolo[3,4-b]pyridin-6(7H)-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridine-3-sulfonamide (0.180 g, 0.324 mmol) was dissolved in TFA (2.00 mL, 26.0 mmol) and heated at 70° C. for 2 h. The volatile components were removed under reduced pressure and resulting residue was diluted with saturated NaHCO3 (30 mL). The reaction mixture was extracted with EtOAc (3×50 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was purified by preparative HPLC (Condition B-98 as described in general methods) to afford 2-methoxy-5-(5-phenyl-4-(5H-pyrrolo[3,4-b]pyridin-6(7H)-yl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridine-3-sulfonamide (32.0 mg, 19.8%) as off-white solid. LCMS Condition B-22: retention time 1.93 min, [M+1]=500.2. HPLC Condition B-31: retention time 9.01 min, purity 97.4%. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.74 (s, 3H), 4.57 (br s, 2H), 4.89 (br s, 2H), 6.83 (d, J=2.7 Hz, 1H), 7.09 (br s, 2H), 7.26 (dd, J=7.8 Hz, J=4.9 Hz, 1H), 7.37-7.43 (m, 1H), 7.44-7.55 (m, 4H), 7.61 (d, J=6.0 Hz, 1H), 7.99 (d, J=2.8 Hz, 1H), 8.38 (d, J=5.1 Hz, 1H), 8.80 (d, J=2.6 Hz, 1H), 8.96 (d, J=2.5 Hz, 1H).

Workup

  1. customThe volatile components were removed under reduced pressure
  2. customresulting residue
  3. extractionThe reaction mixture was extracted with EtOAc (3×50 mL)
  4. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by preparative HPLC (Condition B-98 as described in general methods)

Sources & evidence

ORD record
ord-3ca0e9cad11947bea5f69d0732766fe6
Source dataset
uspto-grants-2015_06
Patent number
US09050345B2

Reaction notes

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