1,2-Dichloroethane → (3aR,7aS)-tert-butyl 5-(3-(3-amino-6-(2,6-difluorophenyl)picolinamido)-pyridin-4-yl)-2-oxohexahydrooxazolo[4,5-c]pyridine-3(2H)-carboxylate

HRID 70000Notes

Reaction equation

HRID 70000 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][C@@H:11]2[O:14][C:15](=[O:24])[N:16]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C@@H:10]2[CH2:9]1.[NH2:25][C:26]1[C:27]([C:40](O)=[O:41])=[N:28][C:29]([C:32]2[C:37]([F:38])=[CH:36][CH:35]=[CH:34][C:33]=2[F:39])=[CH:30][CH:31]=1.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1>CN(C=O)C.O>[NH2:25][C:26]1[C:27]([C:40]([NH:1][C:2]2[CH:3]=[N:4][CH:5]=[CH:6][C:7]=2[N:8]2[CH2:13][CH2:12][C@@H:11]3[O:14][C:15](=[O:24])[N:16]([C:17]([O:19][C:20]([CH3:21])([CH3:23])[CH3:22])=[O:18])[C@@H:10]3[CH2:9]2)=[O:41])=[N:28][C:29]([C:32]2[C:33]([F:39])=[CH:34][CH:35]=[CH:36][C:37]=2[F:38])=[CH:30][CH:31]=1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 181649HOAtHCID 58386808HCID 58386808, compoundHCID 592264283-Amino-6-(2,6-difluorophenyl)picolinic acid

Product 1

HCID 69045136(3aR,7aS)-tert-butyl 5-(3-(3-amino-6-(2,6-difluorophenyl)picolinamido)-pyridin-4-yl)-2-oxohexahydrooxazolo[4,5-c]pyridine-3(2H)-carboxylateYield 46%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (3aR,7aS)-tert-butyl 5-(3-aminopyridin-4-yl)-2-oxohexahydrooxazolo[4,5-c]pyridine-3(2H)-carboxylate (1.0 equiv.) in DMF (0.3 M) was added 3-amino-6-(2,6-difluorophenyl)picolinic acid (1.2 equiv.), EDC (1.2 equiv.) and HOAt (1.2 equiv.). The solution was stirred for 15 h. To the mixture was added water and the precipitate was filtered. To the filtrate was added EtOAc, and the organic solution was extracted (3 times), dried with Na2SO4, and concentrated to give an orange syrup. The crude was triturated with EtOAc and hexanes mixture and the precipitate was filtered off to give pure product in 46% yield. LCMS (m/z): 567.0 (MH+), LC Rt=3.03 min.

Workup

  1. filtrationthe precipitate was filtered
  2. additionTo the filtrate was added EtOAc
  3. extractionthe organic solution was extracted (3 times)
  4. dry with materialdried with Na2SO4
  5. concentrationconcentrated
  6. customto give an orange syrup
  7. customThe crude was triturated with EtOAc and hexanes mixture
  8. filtrationthe precipitate was filtered off
  9. customto give pure product in 46% yield

Sources & evidence

ORD record
ord-0b2ecad9216b4a58ab1752febb3c391c
Source dataset
uspto-grants-2014_09
Patent number
US08822497B2

Reaction notes

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