1,2-Dichloroethane → (3aR,7aS)-tert-butyl 5-(3-(3-amino-6-(2-fluoro-5-(isopropylcarbamoyl)phenyl)picolinamido)pyridin-4-yl)-2-oxohexahydro-oxazolo[4,5-c]pyridine-3(2H)-carboxylate

HRID 70001Notes

Reaction equation

HRID 70001 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:45](O)=[O:46])=[N:28][C:29]([C:32]2[CH:37]=[C:36]([C:38](=[O:43])[NH:39][CH:40]([CH3:42])[CH3:41])[CH:35]=[CH:34][C:33]=2[F:44])=[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:45]([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:46])=[N:28][C:29]([C:32]2[CH:37]=[C:36]([C:38](=[O:43])[NH:39][CH:40]([CH3:42])[CH3:41])[CH:35]=[CH:34][C:33]=2[F:44])=[CH:30][CH:31]=1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 181649HOAtHCID 58386808HCID 58386808, compoundHCID 690434223-Amino-6-(2-fluoro-5-(isopropylcarbamoyl)phenyl)picolinic acid

Product 1

HCID 69044431(3aR,7aS)-tert-butyl 5-(3-(3-amino-6-(2-fluoro-5-(isopropylcarbamoyl)phenyl)picolinamido)pyridin-4-yl)-2-oxohexahydro-oxazolo[4,5-c]pyridine-3(2H)-carboxylate

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-fluoro-5-(isopropylcarbamoyl)phenyl)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 (3aR,7aS)-tert-butyl 5-(3-(3-amino-6-(2-fluoro-5-(isopropylcarbamoyl)phenyl)picolinamido)pyridin-4-yl)-2-oxohexahydro-oxazolo[4,5-c]pyridine-3(2H)-carboxylate. LCMS (m/z): 634.3.

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

Sources & evidence

ORD record
ord-34a26910649f4c5da32cfca7d7053d9e
Source dataset
uspto-grants-2014_09
Patent number
US08822497B2

Reaction notes

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