Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1) → 1-{5-tert-Butyl-2-[3-(2-hydroxy-ethoxy)-phenyl]-2H-pyrazol-3-yl}-3-[(1S,4R)-4-(3-diisopropylamino-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea

HRID 630880Notes

Reaction equation

HRID 630880 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([NH:26][C:27]([NH:29][C@@H:30]2[C:39]3[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=3)[C@H:33]([O:40][C:41]3[CH:42]=[CH:43][C:44]4[N:45]([C:47]([N:50]([CH:54]([CH3:56])[CH3:55])[CH:51]([CH3:53])[CH3:52])=[N:48][N:49]=4)[CH:46]=3)[CH2:32][CH2:31]2)=[O:28])[N:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH2:17][CH2:18][O:19]C3CCCCO3)[CH:11]=2)[N:9]=1)([CH3:4])([CH3:3])[CH3:2].C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>CO>[C:1]([C:5]1[CH:6]=[C:7]([NH:26][C:27]([NH:29][C@@H:30]2[C:39]3[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=3)[C@H:33]([O:40][C:41]3[CH:42]=[CH:43][C:44]4[N:45]([C:47]([N:50]([CH:51]([CH3:53])[CH3:52])[CH:54]([CH3:55])[CH3:56])=[N:48][N:49]=4)[CH:46]=3)[CH2:32][CH2:31]2)=[O:28])[N:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH2:17][CH2:18][OH:19])[CH:11]=2)[N:9]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 86687167HCID 86687167, compound

Product 1

HCID 866871681-{5-tert-Butyl-2-[3-(2-hydroxy-ethoxy)-phenyl]-2H-pyrazol-3-yl}-3-[(1S,4R)-4-(3-diisopropylamino-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-ureaYield 109.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of Intermediate 103d (100 mg, 0.13 mmol) in MeOH (2 mL) was added pyridinium p-toluenesulfonate (65 mg, 0.26 mmol) and the reaction mixture was heated to reflux temperature for 3 h. The volatiles were concentrated in vacuo and the resultant residue was partitioned between EtOAc and water. The aqueous phase was extracted with EtOAc (×3) and the combined organic layers were washed with brine, dried (MgSO4) and concentrated in vacuo to afford the title compound (97 mg, 99%). LCMS (Method 2): Rt 3.39 min, m/z 681 [MH+].

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux temperature for 3 h
  3. concentrationThe volatiles were concentrated in vacuo
  4. customthe resultant residue was partitioned between EtOAc and water
  5. extractionThe aqueous phase was extracted with EtOAc (×3)
  6. washthe combined organic layers were washed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b007e0b8d0e2440e9854496e4f4a5997
Source dataset
uspto-grants-2016_04
Patent number
US09315503B2

Reaction notes

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