Hydrochloric Acid → HCID 89544203, compound

HRID 2283436Notes

Reaction equation

HRID 2283436 reaction equation
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9]([NH:12][CH2:13][CH:14](C)[C:15]([NH2:17])=[O:16])[CH2:10][CH3:11])=[C:5]([F:19])[C:4]=1[C:20]([C:22]1[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=1)=[O:21].[OH-].[Na+].C([NH2:34])(=O)C=C.Cl>C(O)C.O.C(Cl)Cl>[NH2:34][C:25]1[N:24]=[CH:23][C:22]([C:20]([C:4]2[C:5]([F:19])=[C:6]([C@H:9]([NH:12][CH2:13][CH2:14][C:15]([NH2:17])=[O:16])[CH2:10][CH3:11])[CH:7]=[CH:8][C:3]=2[Cl:2])=[O:21])=[CH:27][CH:26]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6579Acrylamide2×HCID 14798Sodium HydroxideHCID 131733523HCID 131733523, compound

Product 1

HCID 89544203HCID 89544203, compoundYield 25.9%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

Example 1 (200 mg, 0.58 mmol) was partitioned between DCM (5 mL) and water (3 mL) basified to pH 12 with 5M NaOH. The organic phase was isolated by phase separator and blown down into a microwave vial. Acrylamide (41 mg, 0.58 mmol, 1 eq.) and MnCl2.4H2O (57 mg, 0.29 mmol, 0.5 eq.) was heated in ethanol (0.9 mL) and water (0.1 mL) in the microwave at 100 degC for 30 min. Only partial reaction, so further acrylamide and MnCl2 (same amounts) were added and the reaction heated for 30 min at 100° C. Still not complete so reaction heated as is for another 30 min at 100° C. The mixture then partitioned between EtOAc (15 mL) and water (10 mL) (plus drop of 5M NaOH) and then the aqueous extracted with further EtOAc (15 mL). Combined organics were washed with water (10 mL) and brine (10 mL) and then dried (MgSO+), filtered and concentrated. Purified by chiral HPLC normal phase, eluting EtOH and heptane. Concentrated and then dissolved in DCM (2 mL) and 1.1 eq. 2M HCl in Et2O added. Concentrated and dried in a vacuum oven to give 3-{[(1R)-1-{3-[(6-aminopyridin-3-yl)carbonyl]-4-chloro-2-fluorophenyl}propyl]amino}-propanamide (56 mg, 0.15 mmol, 25%) as an HCl salt and white solid.

Workup

  1. customThe organic phase was isolated by phase separator
  2. customOnly partial reaction
  3. customStill not complete so reaction
  4. temperatureheated
  5. customThe mixture then partitioned between EtOAc (15 mL) and water (10 mL) (plus drop of 5M NaOH)
  6. extractionthe aqueous extracted with further EtOAc (15 mL)
  7. washCombined organics were washed with water (10 mL) and brine (10 mL)
  8. dry with materialdried (MgSO+)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customPurified by chiral HPLC normal phase
  12. washeluting EtOH and heptane
  13. concentrationConcentrated
  14. dissolutiondissolved in DCM (2 mL)
  15. addition2M HCl in Et2O added
  16. concentrationConcentrated
  17. customdried in a vacuum oven

Sources & evidence

ORD record
ord-0e554bd3eb584b1799cd16a0c9aeb004
Source dataset
uspto-grants-2015_09
Patent number
US09145354B2

Reaction notes

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