Pyridine → (1S,4S)-2-Oxa-5-aza-bicyclo[2.2.1]heptane-5-carboxylic Acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide

HRID 1744814Notes

Reaction equation

HRID 1744814 reaction equation
[CH3:1][O:2][C:3]1[C:8]2[N:9]=[C:10]([NH2:12])[S:11][C:7]=2[C:6]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[CH:5][CH:4]=1.N1C=CC=CC=1.Cl[C:26](OC1C=CC=CC=1)=[O:27].[C@H:35]12[CH2:41][C@H:38]([NH:39][CH2:40]1)[CH2:37][O:36]2.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl>[CH3:1][O:2][C:3]1[C:8]2[N:9]=[C:10]([NH:12][C:26]([N:39]3[CH2:40][C@@H:35]4[CH2:41][C@H:38]3[CH2:37][O:36]4)=[O:27])[S:11][C:7]=2[C:6]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[CH:5][CH:4]=1

Participants

7

Reactant 5

HCID 1049PyridineHCID 10340Sodium CarbonateHCID 15891Phenyl chloroformateHCID 11159293(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptane hydrobromideHCID 114028614-Methoxy-7-morpholinobenzo[d]thiazol-2-amine

Product 1

HCID 11188451(1S,4S)-2-Oxa-5-aza-bicyclo[2.2.1]heptane-5-carboxylic Acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amideYield 35%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-methoxy-7-morpholin-4-yl-benzothiazol-2-ylamine (265 mg, 1.0 mmol) in dichloromethane (15 ml) is subsequently added pyridine (0.24 ml, 3.0 mmol) and phenyl chloroformate (0.15 ml, 1.2 mmol) and the resulting solution stirred for 45 min at ambient temperature. Then (1S,4S)-2-oxa-5-aza-bicyclo[2.2.1]heptane (490 mg, 3.6 mmol) is added and the mixture stirred at ambient temperature for 15 min and at 40° C. for 2.5 h. After cooling to ambient temperature, saturated aqueous sodium carbonate (15 ml) is added, the organic phase is separated, dryed and the solvent evaporated in vacuo. Flash chromatography (silica, eluent: dichloromethane containing methanol (gradient from 0 to 5%)) afforded the title compound as white crystals (135 mg, 35% yield). MS: m/e=391(M+H+).

Workup

  1. stirringthe mixture stirred at ambient temperature for 15 min and at 40° C. for 2.5 h
  2. temperatureAfter cooling to ambient temperature
  3. customthe organic phase is separated
  4. customthe solvent evaporated in vacuo
  5. additionFlash chromatography (silica, eluent: dichloromethane containing methanol (gradient from 0 to 5%))

Sources & evidence

ORD record
ord-ad29433b1f2d4bd8ac4302f564cf4b9b
Source dataset
uspto-grants-2006_03
Patent number
US07019001B2

Reaction notes

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