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

HRID 630976Notes

Reaction equation

HRID 630976 reaction equation
[Si]([O:18][CH2:19][C:20]([C:23]1[CH:27]=[C:26]([NH:28][C:29]([NH:31][C@@H:32]2[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[C@H:35]([O:42][C:43]3[CH:44]=[CH:45][C:46]4[N:47]([C:49]([N:52]5[CH2:57][CH2:56][CH2:55][CH2:54][C@@H:53]5[CH3:58])=[N:50][N:51]=4)[CH:48]=3)[CH2:34][CH2:33]2)=[O:30])[N:25]([C:59]2[CH:64]=[CH:63][CH:62]=[C:61]([O:65][CH2:66][CH2:67][O:68][CH:69]3CCCC[O:70]3)[CH:60]=2)[N:24]=1)([CH3:22])[CH3:21])(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+:86]1[CH:91]=CC=C[CH:87]=1>CO>[CH:69]([OH:70])=[O:68].[CH3:87][N:86]([CH3:91])[CH2:67][CH2:66][O:65][C:61]1[CH:60]=[C:59]([N:25]2[C:26]([NH:28][C:29]([NH:31][C@@H:32]3[C:41]4[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=4)[C@H:35]([O:42][C:43]4[CH:44]=[CH:45][C:46]5[N:47]([C:49]([N:52]6[CH2:57][CH2:56][CH2:55][CH2:54][C@@H:53]6[CH3:58])=[N:50][N:51]=5)[CH:48]=4)[CH2:34][CH2:33]3)=[O:30])=[CH:27][C:23]([C:20]([CH3:22])([CH3:21])[CH2:19][OH:18])=[N:24]2)[CH:64]=[CH:63][CH:62]=1

Participants

4

Reactant 2

HCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 86687288HCID 86687288, compound

Product 1

HCID 1176659601-[2-[3-(2-Dimethylamino-ethoxy)-phenyl]-5-(2-hydroxy-1,1-dimethyl-ethyl)-2H-pyrazol-3-yl]-3-{(1S,4R)-4-[3-((S)-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate saltYield 91.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
45 °C

Procedure

A solution of Intermediate 153g (317 mg, 0.31 mmol) in MeOH (3.1 mL) was treated with pyridinium para-toluenesulfonate (235 mg, 0.93 mmol) and the mixture was stirred at 45° C. for 19 h. The cooled solution was concentrated in vacuo, and the residue was partitioned between DCM and a saturated aqueous sodium bicarbonate solution. The phases were separated and the aqueous layer was extracted with DCM (×2). The combined organic phase was washed with water, a saturated aqueous sodium bicarbonate solution, and brine, dried (Na2SO4) and concentrated in vacuo to a cream coloured foam. The foam was purified by FCC, using 0-10% MeOH in DCM, to give the title compound as a colourless glass (217 mg, 75%). LCMS (Method 3): Rt 5.06 min, ink 933.7 [MH+].

Workup

  1. concentrationThe cooled solution was concentrated in vacuo
  2. customthe residue was partitioned between DCM
  3. customThe phases were separated
  4. extractionthe aqueous layer was extracted with DCM (×2)
  5. washThe combined organic phase was washed with water
  6. dry with materiala saturated aqueous sodium bicarbonate solution, and brine, dried (Na2SO4)
  7. concentrationconcentrated in vacuo to a cream
  8. customThe foam was purified by FCC

Sources & evidence

ORD record
ord-409a627243dc4c22a7e871878b909a44
Source dataset
uspto-grants-2016_04
Patent number
US09315503B2

Reaction notes

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