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

HRID 60686Notes

Reaction equation

HRID 60686 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([NH:27][C:28]([NH:30][C@@H:31]2[C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[C@H:34]([O:41][C:42]3[CH:43]=[CH:44][C:45]4[N:46]([C:48]([N:51]5[CH2:55][CH2:54][CH2:53][C@@H:52]5[CH3:56])=[N:49][N:50]=4)[CH:47]=3)[CH2:33][CH2:32]2)=[O:29])[N:8]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([O:17][CH2:18][CH2:19][O:20]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(Cl)Cl>[C:1]([C:5]1[CH:6]=[C:7]([NH:27][C:28]([NH:30][C@@H:31]2[C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[C@H:34]([O:41][C:42]3[CH:43]=[CH:44][C:45]4[N:46]([C:48]([N:51]5[CH2:55][CH2:54][CH2:53][C@@H:52]5[CH3:56])=[N:49][N:50]=4)[CH:47]=3)[CH2:33][CH2:32]2)=[O:29])[N:8]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([O:17][CH2:18][CH2:19][OH:20])[CH:11]=2)[N:9]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 1177298451-(5-tert-Butyl-2-{4-chloro-3-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-phenyl}-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-((S)-2-methyl-pyrrolidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea

Product 1

HCID 1177296161-{5-tert-Butyl-2-[4-chloro-3-(2-hydroxy-ethoxy)-phenyl]-2H-pyrazol-3-yl}-3-{(1S,4R)-4-[3-((S)-2-methyl-pyrrolidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureaYield 78%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of Intermediate 78c (60.0 mg, 0.08 mmol) and pyridinium p-toluene sulphonate (58.0 mg, 0.23 mmol) in MeOH (1 mL) was heated at 45° C. for 18 h. The reaction mixture was cooled and diluted with DCM (5 mL). This was washed with sat. aq. NaHCO3 (2×5 mL). The organic layer was passed through a phase separator and concentrated in vacuo. The residue was purified by FCC, using 0-10% MeOH in DCM, to afford the title compound (42 mg, 78%). LCMS (Method 3): Rt: 3.47 min, m/z 699/701 [MH+].

Workup

  1. temperatureThe reaction mixture was cooled
  2. washThis was washed with sat. aq. NaHCO3 (2×5 mL)
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-1b6cfc90313d4d908a2cfd811ee69d7d
Source dataset
uspto-grants-2016_09
Patent number
US09440974B2

Reaction notes

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