Water → Methanesulfonic acid 2-{3-[3-tert-butyl-5-(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}-ureido)-pyrazol-1-yl]-phenoxy}-ethyl ester

HRID 1402443Notes

Reaction equation

HRID 1402443 reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[C:6]([C:10]1[CH:11]=[C:12]([NH:25][C:26]([NH:28][C@@H:29]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[C@H:32]([O:39][C:40]3[CH:41]=[CH:42][C:43]4[N:44]([C:46]([N:49]5[CH2:54][CH2:53][CH2:52][CH2:51][C@@H:50]5[CH3:55])=[N:47][N:48]=4)[CH:45]=3)[CH2:31][CH2:30]2)=[O:27])[N:13]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH2:22][CH2:23][OH:24])[CH:16]=2)[N:14]=1)([CH3:9])([CH3:8])[CH3:7].CCN(C(C)C)C(C)C.O>C(Cl)Cl>[C:6]([C:10]1[CH:11]=[C:12]([NH:25][C:26]([NH:28][C@@H:29]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[C@H:32]([O:39][C:40]3[CH:41]=[CH:42][C:43]4[N:44]([C:46]([N:49]5[CH2:54][CH2:53][CH2:52][CH2:51][C@@H:50]5[CH3:55])=[N:47][N:48]=4)[CH:45]=3)[CH2:31][CH2:30]2)=[O:27])[N:13]([C:15]2[CH:16]=[C:17]([CH:18]=[CH:19][CH:20]=2)[O:21][CH2:22][CH2:23][O:24][S:2]([CH3:1])(=[O:4])=[O:3])[N:14]=1)([CH3:9])([CH3:7])[CH3:8]

Participants

6

Reactant 4

HCID 962WaterHCID 31297Methanesulfonyl chloride2×HCID 81531DiisopropylethylamineHCID 866872061-{5-tert-Butyl-2-[3-(2-hydroxy-ethoxy)-phenyl]-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

Product 1

HCID 86687292Methanesulfonic acid 2-{3-[3-tert-butyl-5-(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}-ureido)-pyrazol-1-yl]-phenoxy}-ethyl esterYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methanesulfonyl chloride (81 μL, 1.05 mmol) was added to a stirred solution of Intermediate 95e (545 mg, 803 mmol) and DIPEA (420 μL, 2.41 mmol) in DCM (20 mL), under argon and the reaction mixture was stirred at RT for 1.5 h. A further 25 μL, 0.32 mmol of methanesulfonyl chloride was added and the reaction mixture continued to stir at RT for 2 h. Water (20 mL) was added and the two layers were shaken thoroughly before being separated. The aqueous layer was extracted with DCM (2×20 mL) and the combined organics were passed through a phase separator and concentrated in vacuo to afford the title compound as an orange glass (690 mg, >100%). LCMS (Method 3): Rt 3.89 min, m/z 757 [MH+].

Workup

  1. stirringto stir at RT for 2 h
  2. stirringthe two layers were shaken thoroughly
  3. custombefore being separated
  4. extractionThe aqueous layer was extracted with DCM (2×20 mL)
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ee511491f12b4060be4e2b45bd7d6888
Source dataset
uspto-grants-2014_12
Patent number
US08907094B2

Reaction notes

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