HCID 78035251, compound → HCID 71486743, compound

HRID 1422606Notes

Reaction equation

HRID 1422606 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:10][C:11]2[CH:12]=[CH:13][C:14]([F:33])=[C:15]([C:17]34[CH2:24][CH:23]3[CH2:22][CH2:21][S:20][C:19]([NH:25]C(=O)OC(C)(C)C)=[N:18]4)[CH:16]=2)=[O:9])=[N:6][CH:7]=1>ClCCl.FC(F)(F)C(O)=O>[NH2:25][C:19]1[S:20][CH2:21][CH2:22][CH:23]2[C:17]([C:15]3[CH:16]=[C:11]([NH:10][C:8]([C:5]4[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][N:6]=4)=[O:9])[CH:12]=[CH:13][C:14]=3[F:33])([CH2:24]2)[N:18]=1

Participants

4

Reactant 1

HCID 78035251HCID 78035251, compound

Product 1

HCID 71486743HCID 71486743, compoundYield 58%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
23 °C

Procedure

tert-Butyl (1SR,7SR)-1-(5-(5-chloropicolinamido)-2-fluorophenyl)-4-thia-2-azabicyclo[5.1.0]oct-2-en-3-ylcarbamate (intermediate rac-A9a) (29 mg; 0.06 mmol) was dissolved in dichloromethane (3 ml) and at 23° C. trifluoroacetic acid (TFA) (0.8 ml) was added. The yellow solution was stirred for 2 hours at 23° C. The reaction mixture was extracted with sat NaHCO3 solution and dichloromethane. The organic layer was washed with water and brine, the aqueous layers were reextracted with dichloromethane. The combined organic layers were dried over Na2SO4, filtered and evaporated to give a light yellow oil which was chromatographed on 10 g SiO2—NH2 with dichloromethane+dichloromethane/methanol 19:1 to give the 5-chloro-pyridine-2-carboxylic acid [3-((1SR,7SR)-3-amino-4-thia-2-aza-bicyclo[5.1.0]oct-2-en-1-yl)-4-fluoro-phenyl]-amide (13.34 mg; 58%) as an off white solid. MS (ISP): m/z=391.0 [(M+H)+] and 393.1 [(M+2+H)+].

Workup

  1. additionwas added
  2. extractionThe reaction mixture was extracted with sat NaHCO3 solution and dichloromethane
  3. washThe organic layer was washed with water and brine
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customto give a light yellow oil which
  8. customwas chromatographed on 10 g SiO2—NH2 with dichloromethane+dichloromethane/methanol 19:1

Sources & evidence

ORD record
ord-7a33f2b64a6349069c62d766392507a3
Source dataset
uspto-grants-2015_01
Patent number
US08927535B2

Reaction notes

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