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

HRID 2404464Notes

Reaction equation

HRID 2404464 reaction equation
I[C:2]1[CH:3]=[C:4]([CH:8]([O:18][CH:19]2[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]2)[C:9]2[S:10][C:11]3[CH:17]=[CH:16][CH:15]=[CH:14][C:12]=3[N:13]=2)[CH:5]=[CH:6][CH:7]=1.C(C1CCCCC1=O)(=O)C(C)C.C(=O)([O-])[O-].[Cs+].[Cs+].[C:44]([NH:51][CH:52]1[CH2:56][CH2:55][NH:54][CH2:53]1)([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45]>[Cu]I.CN(C)C=O>[C:47]([O:46][C:44](=[O:45])[NH:51][CH:52]1[CH2:56][CH2:55][N:54]([C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([CH:8]([C:9]3[S:10][C:11]4[CH:17]=[CH:16][CH:15]=[CH:14][C:12]=4[N:13]=3)[O:18][CH:19]3[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]3)[CH:3]=2)[CH2:53]1)([CH3:50])([CH3:48])[CH3:49]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 2757234tert-butyl N-(pyrrolidin-3-yl)carbamateHCID 114693012-(2-Methylpropanoyl)cyclohexan-1-oneHCID 569474582-[(3-Iodophenyl)(1-methylpiperidin-4-yloxy)methyl]benzothiazole

Product 1

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

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

A screw-capped tube is charged with 2-[(3-iodophenyl)(1-methylpiperidin-4-yloxy)methyl]benzothiazole (example 41, 200 mg), copper(I) iodide (7 mg), 2-isobutyrylcyclohexanone (25 mg), cesium carbonate (280 mg), 3-(Boc-amino)pyrrolidine (160 mg) and anhydrous N,N-dimethylformamide (1 mL). The tube is evacuated, filled with argon and sealed. After stirring at 55° C. for 4 days, the mixture is diluted with ethyl acetate, water and ammonia. After decantation, the aqueous phase is extracted with ethyl acetate. The pooled organic extracts are dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by chromatography (gradient dichloromethane/methanol/ammonia from 98/2/0.5 to 95/5/0.5), to afford (1-{3-[benzothiazol-2-yl-(1-methylpiperidin-4-yloxy)methyl]phenyl}pyrrolidin-3-yl)carbamic acid tert-butyl ester.

Workup

  1. customThe tube is evacuated
  2. additionfilled with argon
  3. customsealed
  4. additionthe mixture is diluted with ethyl acetate, water and ammonia
  5. extractionAfter decantation, the aqueous phase is extracted with ethyl acetate
  6. dry with materialThe pooled organic extracts are dried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue is purified by chromatography (gradient dichloromethane/methanol/ammonia from 98/2/0.5 to 95/5/0.5)

Sources & evidence

ORD record
ord-e606802f4fcd4340861a1190a29cda1b
Source dataset
uspto-grants-2014_08
Patent number
US08802664B2

Reaction notes

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