Diisopropylethylamine → (S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-N-((1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((R)-piperidin-2-yl)propan-2-yl)-4-phenylbutanamide

HRID 132950Notes

Reaction equation

HRID 132950 reaction equation
COC1C=[CH:55][C:6]([CH2:7][N:8]2C[C@H](OCC=C)[CH2:10][C@@H:9]2[C@@H:17]([OH:54])[C@@H:18]([NH:28]C(=O)[C@@H](N2CC[C@](NC(=O)C)(CC(C)C)C2=O)CCC2C=CC=CC=2)[CH2:19][C:20]2[CH:25]=[C:24]([F:26])[CH:23]=[C:22]([F:27])[CH:21]=2)=CC=1.[C:57]([NH:60][C@:61]1([C@@H:110]([CH2:112][CH3:113])[CH3:111])[CH2:65][CH2:64][N:63]([C@@H:66]([CH2:101][CH2:102][C:103]2[CH:108]=[CH:107][CH:106]=[CH:105][CH:104]=2)[C:67](N[C@@H](CC2C=C(F)C=C(F)C=2)[C@@H]([C@H]2CCCCN2C(C2C=CC=CC=2)C2C=CC=CC=2)O)=[O:68])[C:62]1=[O:109])(=[O:59])[CH3:58].C(N[C@]1([C@@H](CC)C)CCN([C@@H](CCC2C=CC=CC=2)C(O)=O)C1=O)(=O)C.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.N[C@@H](CC1C=C(F)C=C(F)C=1)[C@@H]([C@H]1CCCCN1C(C1C=CC=CC=1)C1C=CC=CC=1)O>ClCCl>[C:57]([NH:60][C@:61]1([C@@H:110]([CH2:112][CH3:113])[CH3:111])[CH2:65][CH2:64][N:63]([C@@H:66]([CH2:101][CH2:102][C:103]2[CH:104]=[CH:105][CH:106]=[CH:107][CH:108]=2)[C:67]([NH:28][C@@H:18]([CH2:19][C:20]2[CH:21]=[C:22]([F:27])[CH:23]=[C:24]([F:26])[CH:25]=2)[C@H:17]([OH:54])[C@H:9]2[CH2:10][CH2:55][CH2:6][CH2:7][NH:8]2)=[O:68])[C:62]1=[O:109])(=[O:59])[CH3:58]

Participants

8

Reactant 6

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58608199(1S,2S)-2-amino-1-((R)-1-benzhydrylpiperidin-2-yl)-3-(3,5-difluorophenyl)propan-1-olHCID 67270863(S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-4-phenylbutanoic acidHCID 69194179(S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-N-((1S,2S)-1-((R)-1-benzhydrylpiperidin-2-yl)-3-(3,5-difluorophenyl)-1-hydroxypropan-2-yl)-4-phenylbutanamideHCID 69195642(S)-N-((1S,2S)-1-((2R,4R)-1-(4-methoxybenzyl)-4-(allyloxy)pyrrolidin-2-yl)-3-(3,5-difluorophenyl)-1-hydroxypropan-2-yl)-2-((R)-3-acetamido-3-isobutyl-2-oxopyrrolidin-1-yl)-4-phenylbutanamide

Product 1

HCID 69195804(S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-N-((1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((R)-piperidin-2-yl)propan-2-yl)-4-phenylbutanamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Step 8 (A): Preparation of (S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-N-((1S,2S)-1-((R)-1-benzhydrylpiperidin-2-yl)-3-(3,5-difluorophenyl)-1-hydroxypropan-2-yl)-4-phenylbutanamide. To a solution of (S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-4-phenylbutanoic acid (Preparation A, 45 mg, 0.126 mmol) in dichloromethane (3 mL) was added Hunig's base (45 mg, 0.38 mmol) to make a clear solution and HATU (62 mg, 0.164 mmol) was then added. After stirring for 20 min, the reaction mixture was added (1S,2S)-2-amino-1-((R)-1-benzhydrylpiperidin-2-yl)-3-(3,5-difluorophenyl)propan-1-ol (Preparation 1,55 mg, 0.126 mmol) and the reaction mixture was stirred at rt for 6 h. Solvent was removed and the crude mixture was purified by silica gel Flash Chromatography to give 75 mg of the title compound:

Workup

  1. additionwas then added
  2. stirringthe reaction mixture was stirred at rt for 6 h
  3. customSolvent was removed
  4. customthe crude mixture was purified by silica gel Flash Chromatography

Sources & evidence

ORD record
ord-30ae65e687de4fc3b8eaa6b1ff8e9c5b
Source dataset
uspto-grants-2008_06
Patent number
US07388007B2

Reaction notes

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