Diisopropylethylamine → Methyl 2-(6-chloro-4-(isopropylamino)nicotinamido)-3-hydroxypropanoate

HRID 595419Notes

Reaction equation

HRID 595419 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([NH:11][CH:12]([CH3:14])[CH3:13])[C:5]([C:6]([OH:8])=O)=[CH:4][N:3]=1.[NH2:15][CH:16]([CH2:21][OH:22])[C:17]([O:19][CH3:20])=[O:18].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Cl:1][C:2]1[CH:10]=[C:9]([NH:11][CH:12]([CH3:14])[CH3:13])[C:5]([C:6]([NH:15][CH:16]([CH2:21][OH:22])[C:17]([O:19][CH3:20])=[O:18])=[O:8])=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 416960Methyl DL-serinateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 896898576-Chloro-4-(isopropylamino)nicotinic acid

Product 1

HCID 89689704Methyl 2-(6-chloro-4-(isopropylamino)nicotinamido)-3-hydroxypropanoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 6-chloro-4-(isopropylamino)nicotinic acid (9) (1.3 g, 6.06 mmol) in DMF (25 mL), methyl 2-amino-3-hydroxypropanoate (12.11 mmol) and DIPEA (18.17 mmol) were added followed by the addition of HATU (30.3 mmol) to the reaction mixture and stirred at room temperature for 2 h. DMF was removed under reduced pressure. The residue obtained was diluted with EtOAC and washed with water and 10% NaHCO3 solution. The organic layer was collected, dried over Na2SO4, filtered and concentrated. The crude material obtained was purified by flash chromatography using silica gel and EtOAC: pet ether as eluent to afford the title compound, methyl 2-(6-chloro-4-(isopropylamino)nicotinamido)-3-hydroxypropanoate. LC/MS: ZORBAX SB C18, 4.6×50 mm, 5 μm; Solvent A=10% MeOH: 90% H2O: 0.1% TFA; Solvent B=90% MeOH: 10% H2O: 0.1% TFA; gradient 0-100% B over 2 min (3 min run time); retention time: 1.312 min; LCMS (ES-API), m/z 316.0 (M+H).

Workup

  1. customDMF was removed under reduced pressure
  2. customThe residue obtained
  3. additionwas diluted with EtOAC
  4. washwashed with water and 10% NaHCO3 solution
  5. customThe organic layer was collected
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude material obtained
  10. customwas purified by flash chromatography

Sources & evidence

ORD record
ord-c049cfffa0794d01b9b55a13482be0fc
Source dataset
uspto-grants-2016_01
Patent number
US09242975B2

Reaction notes

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