p-Toluenesulfonic acid → HCID 90004998, compound

HRID 1771400Notes

Reaction equation

HRID 1771400 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([CH2:7][CH2:8][O:9][C:10]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([NH2:19])[CH:17]=3)[NH:12][N:11]=2)[CH2:3][CH2:2]1.[CH3:20][C:21]1[CH:22]=[CH:23][C:24](S(O)(=O)=O)=[CH:25][CH:26]=1.[CH3:31][N:32]([CH:34]=[O:35])C>C1COCC1>[NH2:11][C:10]1[C:22]2[C:21](=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:20]([O:35][C:34]2[CH:2]=[CH:3][N:4]=[C:31]([NH:19][C:16]3[CH:17]=[C:18]4[C:13](=[CH:14][CH:15]=3)[NH:12][N:11]=[C:10]4[O:9][CH2:8][CH2:7][N:4]3[CH2:5][CH2:6][O:1][CH2:2][CH2:3]3)[N:32]=2)=[CH:17][CH:18]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 6228DimethylformamideHCID 90004996HCID 90004996, compound

Product 1

HCID 90004998HCID 90004998, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

A solution of Intermediate E2 (223 mg, 0.738 mmol), 3-(2-morpholinoethoxy)-1H-indazol-5-amine (215 mg, 0.738 mmol) and p-TSA (140 mg, 0.738 mmol) in a mixture of DMF and THF (1:1 v/v, 20 mL) was heated to 90° C. for 6 h and then cooled to RT and maintained at that temperature for a further 64 hr. The reaction mixture was partitioned between saturated aq. NaHCO3 (50 mL) and EtOAc (50 mL). The aq layer was separated and extracted with EtOAc (50 mL) and the combined organic extracts were dried and evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 40 g, 0-10% [0.1% NH3 in MeOH] in DCM, gradient elution) to afford the title compound, Intermediate B17, as a black solid (201 mg, 49%); Rt 1.32 min (Method 2, acidic); m/z 498 (M+H)+ (ES+).

Workup

  1. temperaturecooled to RT
  2. temperaturemaintained at that temperature for a further 64 hr
  3. customThe reaction mixture was partitioned between saturated aq. NaHCO3 (50 mL) and EtOAc (50 mL)
  4. customThe aq layer was separated
  5. extractionextracted with EtOAc (50 mL)
  6. customthe combined organic extracts were dried
  7. customevaporated in vacuo
  8. customThe residue was purified by flash column chromatography (SiO2, 40 g, 0-10% [0.1% NH3 in MeOH] in DCM, gradient elution)

Sources & evidence

ORD record
ord-23b87588ecaf4b9996f37ae00c3ff3dc
Source dataset
uspto-grants-2016_02
Patent number
US09249125B2

Reaction notes

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