Diisopropylethylamine → N-Methyl-L-valinamide

HRID 573006ノート

反応式

HRID 573006 の反応式
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]

参加物

6

反応物 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、化合物2 回HCID 86678337HCID 86678337、化合物2 回

生成物 1

HCID 11423608N-Methyl-L-valinamide

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-e6b19d37d9a74315af2ddaa6d1aeb594
出典データセット
uspto-grants-2015_05
特許番号
US09029406B2

反応ノート

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