Trifluoroacetic acid → 2-(Difluoromethyl)-5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridine-3-sulfonamide

HRID 2170188Notes

Reaction equation

HRID 2170188 reaction equation
C([NH:5][S:6]([C:9]1[C:10]([CH:38]([F:40])[F:39])=[N:11][CH:12]=[C:13]([C:15]2[N:20]=[C:19]([NH:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=3)[C:18]3=[C:29]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)[CH:30]=[CH:31][N:17]3[N:16]=2)[CH:14]=1)(=[O:8])=[O:7])(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:40][CH:38]([F:39])[C:10]1[C:9]([S:6]([NH2:5])(=[O:7])=[O:8])=[CH:14][C:13]([C:15]2[N:20]=[C:19]([NH:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=3)[C:18]3=[C:29]([C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=4)[CH:30]=[CH:31][N:17]3[N:16]=2)=[CH:12][N:11]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90386127N-(tert-Butyl)-2-(difluoromethyl)-5-(5-phenyl-4-((pyridin-2-ylmethyl)amino) pyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridine-3-sulfonamide

Product 1

HCID 903862342-(Difluoromethyl)-5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridine-3-sulfonamideYield 29.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-(tert-Butyl)-2-(difluoromethyl)-5-(5-phenyl-4-((pyridin-2-ylmethyl)amino) pyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridine-3-sulfonamide (0.520 g, 0.923 mmol) was dissolved in CH2Cl2 (4 mL). Then TFA (1.0 0 mL, 13.0 mmol) was added and stirred at RT for 16 h. The volatile components were removed under reduced pressure and the resulting residue was diluted with 10% NaHCO3 (25 mL). The reaction mixture was extracted with EtOAc (2×25 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-96 as described in general methods) to afford 2-(difluoromethyl)-5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridine-3-sulfonamide (0.140 g, 29.9%) as a pale yellow solid. LCMS Condition B-78: retention time 2.29 min, [M+1]=508.2. HPLC Condition B-31: retention time 8.65 min, purity 98.6%. 1H NMR (400 MHz, DMSO-d6) δ ppm 4.95 (d, J=4.8 Hz, 2H), 6.87 (d, J=2.8 Hz, 1H), 7.28-7.62 (m, 9H), 7.75-7.82 (m, 1H), 7.99 (d, J=2.4 Hz, 1H), 8.17 (s, 2H), 8.38-8.40 (m, 1H), 9.09 (d, J=1.6 Hz, 1H), 9.67 (d, J=2.0 Hz, 1H).

Workup

  1. customThe volatile components were removed under reduced pressure
  2. additionthe resulting residue was diluted with 10% NaHCO3 (25 mL)
  3. extractionThe reaction mixture was extracted with EtOAc (2×25 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-96 as described in general methods)

Sources & evidence

ORD record
ord-7a60c614d6884550893dbe28ee8f9587
Source dataset
uspto-grants-2015_06
Patent number
US09050345B2

Reaction notes

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