Diisopropylethylamine → N-Methyl-L-valinamide

HRID 573006Notes

Reaction equation

HRID 573006 reaction equation
C(OC([N:8](C)[C@H:9]([C:13]([NH:15][C@H:16](C(N([C@@H]([C@@H](C)CC)[C@H](OC)CC(O)=O)C)=O)C(C)C)=[O:14])[CH:10]([CH3:12])[CH3:11])=O)(C)(C)C.FC(F)(F)C(O)=O.C(OC(=O)[C@H](C)[C@@H](OC)[C@@H]1CCCN1)C1C=CC=CC=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[CH3:16][NH:15][C:13](=[O:14])[C@H:9]([CH:10]([CH3:12])[CH3:11])[NH2:8]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 70976726HCID 70976726, compound2×HCID 86678337HCID 86678337, compound2×

Product 1

HCID 11423608N-Methyl-L-valinamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1200 mg (2.33 mmol) N-(tert-butoxycarbonyl)-N-methyl-L-valyl-N-[(2R,3S,4S)-1-carboxy-2-methoxy-4-methyl-hexan-3-yl]-N-methyl-L-valinamide (intermediate 5) was combined with 910.8 mg (2.33 mmol) benzyl-(2R,3R)-3-methoxy-2-methyl-3-[(2S)-pyrrolidin-2-yl]propanoate trifluoroacetic acid salt (intermediate 6), 1327 mg (3.49 mmol) O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate and 2027 μL N,N-diisopropylethylamine in 50 mL DMF and stirred for 5 min at RT. Next the solvent was removed in vacuo. The remaining residue was dissolved in ethyl acetate and then extracted with 5% aqueous citric acid solution and saturated sodium bicarbonate solution in succession. The organic phase was separated and concentrated. The residue was purified by preparative HPLC. The product fractions were combined, concentrated and the residue was dried in a high vacuum, yielding 1000 mg (55% of the theoretical) of the benzyl ester intermediate N-(tert-butoxycarbonyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-benzyloxy)-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide as a resin.

Workup

  1. customNext the solvent was removed in vacuo
  2. dissolutionThe remaining residue was dissolved in ethyl acetate
  3. extractionextracted with 5% aqueous citric acid solution and saturated sodium bicarbonate solution in succession
  4. customThe organic phase was separated
  5. concentrationconcentrated
  6. customThe residue was purified by preparative HPLC
  7. concentrationconcentrated
  8. customthe residue was dried in a high vacuum

Sources & evidence

ORD record
ord-e6b19d37d9a74315af2ddaa6d1aeb594
Source dataset
uspto-grants-2015_05
Patent number
US09029406B2

Reaction notes

Loading…