Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1) → HCID 86344438, compound

HRID 60643Notes

Reaction equation

HRID 60643 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[CH2:56][CH2:55][CH2:54][CH2:53][CH2:52]5)=[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: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[CH2:56][CH2:55][CH2:54][CH2:53][CH2:52]5)=[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

4

Reactant 2

HCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 1177296801-(5-tert-Butyl-2-{4-chloro-3-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-phenyl}-2H-pyrazol-3-yl)-3-[(1S,4R)-4-(3-piperidin-1-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea

Product 1

HCID 86344438HCID 86344438, compoundYield 83%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of Intermediate 53c (830 mg, 1.06 mmol) and pyridinium p-toluenesulphonate (799 mg, 3.18 mmol) in methanol (7 mL) was stirred at 40-45° C. for 18.5 h. The cooled mixture was concentrated in vacuo, diluted with sat. sodium hydrogen carbonate solution and extracted with DCM (3×15 mL). The combined organics were dried and concentrated in vacuo. The residue was purified by FCC, using 0-12% MeOH in DCM, to give the product as a solid (613 mg, 83%). An aliquot (50 mg) was further purified by HPLC (XBridge C18 column, 30-90% MeCN in H2O, 0.1% NH4OH) to give the title compound (38 mg). LCMS (Method 5): Rt 4.42 min, m/z 699.5 [MH+]. 1H NMR (400 MHz, d6-DMSO): 1.28 (9H, s), 1.57-1.65 (2H, m), 1.68-1.77 (4H, m), 1.80-1.97 (2H, m), 1.98-2.17 (2H, m), 3.11-3.17 (4H, m), 3.74 (2H, q, J=5.0 Hz), 4.12 (2H, t, J=5.0 Hz), 4.76-4.85 (1H, m), 4.90 (1H, t, J=5.1 Hz), 5.54 (1H, t, J=4.3 Hz), 6.34 (1H, s), 7.05-7.11 (2H, m), 7.16 (1H, dd, J=2.0, 9.9 Hz), 7.21-7.41 (5H, m), 7.54 (1H, d, J=8.5 Hz), 7.59-7.65 (2H, m), 8.14 (1H, br s).

Workup

  1. concentrationThe cooled mixture was concentrated in vacuo
  2. additiondiluted with sat. sodium hydrogen carbonate solution
  3. extractionextracted with DCM (3×15 mL)
  4. customThe combined organics were dried
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-f260794ba06e44a3aed1a9bbd6a22857
Source dataset
uspto-grants-2016_09
Patent number
US09440974B2

Reaction notes

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