Methanesulfonyl chloride → HCID 86662232, compound

HRID 1627302Notes

Reaction equation

HRID 1627302 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:10]=[C:11]([F:39])[C:12]=1[CH2:13][S:14][C:15]1[N:16]([C:32]2[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=2)[C:17]([C:20]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[C:25]([O:30][CH3:31])[CH:24]=2)([CH3:22])[CH3:21])=[CH:18][N:19]=1)[O:5][CH2:6][CH2:7][CH2:8][OH:9].CCN(C(C)C)C(C)C.[CH3:49][S:50](Cl)(=[O:52])=[O:51]>C(Cl)Cl>[CH3:49][S:50]([O:9][CH2:8][CH2:7][CH2:6][O:5][C:4]1[CH:10]=[C:11]([F:39])[C:12]([CH2:13][S:14][C:15]2[N:16]([C:32]3[CH:33]=[CH:34][C:35]([F:38])=[CH:36][CH:37]=3)[C:17]([C:20]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[C:25]([O:30][CH3:31])[CH:24]=3)([CH3:22])[CH3:21])=[CH:18][N:19]=2)=[C:2]([Cl:1])[CH:3]=1)(=[O:52])=[O:51]

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 66740014HCID 66740014, compound

Product 1

HCID 86662232HCID 86662232, compoundYield 99%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 3-(3-chloro-5-fluoro-4-((5-(2-(4-fluoro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)phenoxy)propan-1-ol (420 mg, 0.73 mmol) and DIPEA (0.32 mL, 1.83 mmol) in DCM (10 mL) at 0° C. was added dropwise methanesulfonylchloride (113 μL, 1.45 mmol). After stirring 30 min, the reaction mixture was partitioned in DCM (20 mL) and water (20 mL). The aqueous layer was re-extracted with DCM (20 mL×2). The combined organic layers were dried over MgSO4, concentrated and purified by column chromatography (EtOAc/Hex=1:2) to give 3-(3-chloro-5-fluoro-4-((5-(2-(4-fluoro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)phenoxy)propyl methanesulfonate (470 mg, 99% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.25 (d, J=8.65 Hz, 1H), 6.87 (dd, J=11.04, 8.48 Hz, 1H), 6.81-6.73 (m, 2H), 6.69-6.66 (m, 1H), 6.58 (dd, J=8.13, 2.23 Hz, 1H), 6.50-6.43 (m, 2H), 6.38-6.31 (m, 1H), 4.42 (t, J=6.04 Hz, 2H), 4.18 (s, 2H), 4.03 (t, J=5.88 Hz, 2H), 3.77 (d, J=5.83 Hz, 2H), 3.68 (s, 4H), 3.10-2.98 (m, 3H), 2.22 (p, J=5.94 Hz, 2H), 1.51 (t, J=4.73 Hz, 5H).

Workup

  1. customthe reaction mixture was partitioned in DCM (20 mL)
  2. extractionThe aqueous layer was re-extracted with DCM (20 mL×2)
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. concentrationconcentrated
  5. custompurified by column chromatography (EtOAc/Hex=1:2)

Sources & evidence

ORD record
ord-86add10530e742339eec68eb9d0d855f
Source dataset
uspto-grants-2014_07
Patent number
US08785488B2

Reaction notes

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