Methanesulfonyl chloride → Methanesulfonic acid 2-{5-[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]-2-triisopropylsilanyloxymethyl-phenoxy}-ethyl ester

HRID 60649Notes

Reaction equation

HRID 60649 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([NH:32][C:33]([NH:35][C@@H:36]2[C:45]3[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=3)[C@H:39]([O:46][C:47]3[CH:48]=[CH:49][C:50]4[N:51]([C:53]([N:56]5[CH2:61][CH2:60][CH2:59][CH2:58][C@@H:57]5[CH3:62])=[N:54][N:55]=4)[CH:52]=3)[CH2:38][CH2:37]2)=[O:34])[N:8]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][O:17][Si:18]([CH:25]([CH3:27])[CH3:26])([CH:22]([CH3:24])[CH3:23])[CH:19]([CH3:21])[CH3:20])=[C:12]([O:28][CH2:29][CH2:30][OH:31])[CH:11]=2)[N:9]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:63][S:64](Cl)(=[O:66])=[O:65].CCN(C(C)C)C(C)C>C(Cl)Cl>[C:1]([C:5]1[CH:6]=[C:7]([NH:32][C:33]([NH:35][C@@H:36]2[C:45]3[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=3)[C@H:39]([O:46][C:47]3[CH:48]=[CH:49][C:50]4[N:51]([C:53]([N:56]5[CH2:61][CH2:60][CH2:59][CH2:58][C@@H:57]5[CH3:62])=[N:54][N:55]=4)[CH:52]=3)[CH2:38][CH2:37]2)=[O:34])[N:8]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][O:17][Si:18]([CH:25]([CH3:27])[CH3:26])([CH:22]([CH3:24])[CH3:23])[CH:19]([CH3:20])[CH3:21])=[C:12]([CH:11]=2)[O:28][CH2:29][CH2:30][O:31][S:64]([CH3:63])(=[O:66])=[O:65])[N:9]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 1235769991-{5-tert-Butyl-2-[3-(2-hydroxy-ethoxy)-4-triisopropylsilanyloxymethyl-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 123589802Methanesulfonic acid 2-{5-[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]-2-triisopropylsilanyloxymethyl-phenoxy}-ethyl esterYield 97.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of Intermediate 55eB (26.0 mg, 0.30 mmol), methanesulfonyl chloride (70.0 μL, 0.90 mmol) and DIPEA (208 μL, 1.20 mmol) in DCM (8 mL) was stirred at RT for 1 h. The reaction mixture was partitioned between DCM and water. The organic layer was washed with brine, separated through a phase separating cartridge and concentrated in vacuo to afford the title compound (275 mg, 97%). LCMS (Method 3): Rt 5.23 min, m/z 943 [MH+].

Workup

  1. customThe reaction mixture was partitioned between DCM and water
  2. washThe organic layer was washed with brine
  3. customseparated through a phase
  4. customseparating cartridge
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c801621156ba44a98938d0274e02daba
Source dataset
uspto-grants-2016_09
Patent number
US09440974B2

Reaction notes

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