Acetic Acid → (S)-1-{(S)-2-[(S)-2-(2-Hydroxy-ethylamino)-propionylamino]-3-methyl-butyryl}-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid phenylamide

HRID 627047Notes

Reaction equation

HRID 627047 reaction equation
[NH2:1][C@@H:2]([CH3:30])[C:3]([NH:5][C@@H:6]([CH:27]([CH3:29])[CH3:28])[C:7]([N:9]1[C:13]2=[N:14][CH:15]=[CH:16][CH:17]=[C:12]2[CH2:11][C@H:10]1[C:18]([NH:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:19])=[O:8])=[O:4].[O:31]1CC(O)O[CH2:33][CH:32]1O.C(O)(=O)C.C([BH3-])#N.[Na+]>CO>[C:21]1([NH:20][C:18]([C@H:10]2[N:9]([C:7](=[O:8])[C@@H:6]([NH:5][C:3](=[O:4])[C@@H:2]([NH:1][CH2:33][CH2:32][OH:31])[CH3:30])[CH:27]([CH3:29])[CH3:28])[C:13]3=[N:14][CH:15]=[CH:16][CH:17]=[C:12]3[CH2:11]2)=[O:19])[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 186078Glycolaldehyde dimerHCID 5003444Sodium cyanoborohydrideHCID 118380538(S)-1-((S)-2-((S)-2-aminopropanamido)-3-methylbutanoyl)-N-phenyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxamide

Product 1

HCID 73603907(S)-1-{(S)-2-[(S)-2-(2-Hydroxy-ethylamino)-propionylamino]-3-methyl-butyryl}-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid phenylamideYield 146.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

In a 50 mL round-bottomed flask, (S)-1-((S)-2-((S)-2-aminopropanamido)-3-methylbutanoyl)-N-phenyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carb ox amide (55 mg, 134 μmol, Eq: 1.00) was combined with MeOH (3 mL) to give a colorless solution. 1,4-Dioxane-2,5-diol (8.87 mg, 73.9 μmol, Eq: 0.55) was added followed by acetic acid (8 μL, 134 μmol, Eq: 1.00) and sodium cyanoborohydride (13 mg, 210 μmol, Eq: 1.5). The reaction was stirred at rt for 4 h and then quenched by dropwise addition of 1 M aqueous HCl. The reaction mixture was basified with 0.1 M aqueous NaOH, extracted with EtOAc, washed with brine, dried over Na2SO4 and concentrated in vacuo to give (S)-1-{(S)-2-[(S)-2-(2-Hydroxy-ethylamino)-propionylamino]-3-methyl-butyryl}-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid phenylamide as a white solid (49 mg), m/z=454.

Workup

  1. customto give a colorless solution
  2. customquenched by dropwise addition of 1 M aqueous HCl
  3. extractionextracted with EtOAc
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-94eb632bffc14bb7b0de6a231836b966
Source dataset
uspto-grants-2016_04
Patent number
US09309248B2

Reaction notes

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