Potassium Carbonate → [2-Amino-5-(3-fluoro-phenyl)-thiazol-4-yl]-((1R,3S,4S)-3-aminomethyl-2-aza-bicyclo[2.2.1]hept-2-yl)-methanone

HRID 882799Notes

Reaction equation

HRID 882799 reaction equation
[NH2:1][C:2]1[S:3][C:4]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=2)=[C:5]([C:7]([N:9]2[C@H:14]([CH2:15][NH:16]C(=O)C(F)(F)F)[C@@H:13]3[CH2:23][C@H:10]2[CH2:11][CH2:12]3)=[O:8])[N:6]=1.C([O-])([O-])=O.[K+].[K+]>CO>[NH2:1][C:2]1[S:3][C:4]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=2)=[C:5]([C:7]([N:9]2[C@H:14]([CH2:15][NH2:16])[C@@H:13]3[CH2:23][C@H:10]2[CH2:11][CH2:12]3)=[O:8])[N:6]=1

Participants

4

Reactant 2

HCID 11430Potassium CarbonateHCID 86649702N-{(1R,3S,4S)-2-[2-Amino-5-(3-fluoro-phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[2.2.1]hept-3-ylmethyl}-2,2,2-trifluoro-acetamide

Product 1

HCID 86649703[2-Amino-5-(3-fluoro-phenyl)-thiazol-4-yl]-((1R,3S,4S)-3-aminomethyl-2-aza-bicyclo[2.2.1]hept-2-yl)-methanone

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

A solution of N-{(1R,3S,4S)-2-[2-Amino-5-(3-fluoro-phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[2.2.1]hept-3-ylmethyl}-2,2,2-trifluoro-acetamide (0.98 mmol) in MeOH (3.2 mL) is treated with a sat. aq. K2CO3 solution (0.3 mL) and stirred at 60° C. for 6 h. After stirring at rt for additional 14 h the mixture is concentrated in vacuo and the residue is made basic by addition of aq. NaOH solution. A 1:1 mixture of TBME and EtOAc is added and the mixture is stirred vigorously for 1 h. The layers are separated and the aq. layer is extracted with a 1:1 mixture of TBME and EtOAc. The combined organic layers are dried over Na2SO4 and concentrated in vacuo to give the desired product which is used without further purification. LC-MS (basic): tR=0.68 min; [M+H]+=347.1.

Workup

  1. stirringAfter stirring at rt for additional 14 h the mixture
  2. concentrationis concentrated in vacuo
  3. additionthe residue is made basic by addition of aq. NaOH solution
  4. additionA 1:1 mixture of TBME and EtOAc
  5. additionis added
  6. stirringthe mixture is stirred vigorously for 1 h
  7. customThe layers are separated
  8. extractionthe aq. layer is extracted with a 1:1 mixture of TBME and EtOAc
  9. dry with materialThe combined organic layers are dried over Na2SO4
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ccd44063386b433ba107622ed9224ebd
Source dataset
uspto-grants-2012_08
Patent number
US08236801B2

Reaction notes

Loading…