(1-{3-[Benzothiazol-2-yl-(1-methylpiperidin-4-yloxy)methyl]phenyl}pyrrolidin-3-yl)carbamic acid tert-butyl ester → HCID 66836079, compound

HRID 572873Notes

Reaction equation

HRID 572873 reaction equation
C(OC(=O)[NH:7][CH:8]1[CH2:12][CH2:11][N:10]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([CH:19]([C:28]3[S:29][C:30]4[CH:36]=[CH:35][CH:34]=[CH:33][C:31]=4[N:32]=3)[O:20][CH:21]3[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]3)[CH:14]=2)[CH2:9]1)(C)(C)C>ClCCl.FC(F)(F)C(O)=O>[S:29]1[C:30]2[CH:36]=[CH:35][CH:34]=[CH:33][C:31]=2[N:32]=[C:28]1[CH:19]([O:20][CH:21]1[CH2:22][CH2:23][N:24]([CH3:27])[CH2:25][CH2:26]1)[C:15]1[CH:14]=[C:13]([N:10]2[CH2:11][CH2:12][CH:8]([NH2:7])[CH2:9]2)[CH:18]=[CH:17][CH:16]=1

Participants

4

Reactant 1

HCID 67512942(1-{3-[Benzothiazol-2-yl-(1-methylpiperidin-4-yloxy)methyl]phenyl}pyrrolidin-3-yl)carbamic acid tert-butyl ester

Product 1

HCID 66836079HCID 66836079, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of crude (1-{3-[benzothiazol-2-yl-(1-methylpiperidin-4-yloxy)methyl]phenyl}pyrrolidin-3-yl)carbamic acid tert-butyl ester (289 mg) in dichloromethane (3 mL) and trifluoroacetic acid (2.5 mL) is stirred at room temperature for one night. The mixture is concentrated under reduced pressure, diluted with ethyl acetate, washed with aqueous 1N sodium hydroxide, dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by chromatography (gradient dichloromethane/methanol/ammonia from 95/5/0.5 to 80/20/0.5). The base is converted into its dioxalate salt in acetone to give 1-{3-[benzothiazol-2-yl(1-methylpiperidin-4-yloxy)methyl]phenyl}pyrrolidin-3-ylamine, dioxalate melting at 145° C.

Workup

  1. concentrationThe mixture is concentrated under reduced pressure
  2. additiondiluted with ethyl acetate
  3. washwashed with aqueous 1N sodium hydroxide
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue is purified by chromatography (gradient dichloromethane/methanol/ammonia from 95/5/0.5 to 80/20/0.5)

Sources & evidence

ORD record
ord-e8d47d700e3a44a189ae5f0a96dee0c0
Source dataset
uspto-grants-2015_05
Patent number
US09029357B2

Reaction notes

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