Diisopropylethylamine → HCID 67272294, compound

HRID 601722Notes

Reaction equation

HRID 601722 reaction equation
[C:1]([NH:4][C@:5]1([C@@H:23]([CH2:25][CH3:26])[CH3:24])[CH2:9][CH2:8][N:7]([C@@H:10]([CH2:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:11](O)=[O:12])[C:6]1=[O:22])(=[O:3])[CH3:2].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.[CH3:60][O:61][C:62]1[CH:91]=[CH:90][C:65]([CH2:66][N:67]2[C@@H:76]([C@@H:77]([OH:89])[C@@H:78]([NH2:88])[CH2:79][C:80]3[CH:85]=[C:84]([F:86])[CH:83]=[C:82]([F:87])[CH:81]=3)[CH2:75][C:74]3[C:69](=[CH:70][CH:71]=[CH:72][CH:73]=3)[CH2:68]2)=[CH:64][CH:63]=1>ClCCl>[CH3:60][O:61][C:62]1[CH:63]=[CH:64][C:65]([CH2:66][N:67]2[C@@H:76]([C@@H:77]([OH:89])[C@@H:78]([NH:88][C:11](=[O:12])[C@@H:10]([N:7]3[CH2:8][CH2:9][C@:5]([NH:4][C:1](=[O:3])[CH3:2])([C@@H:23]([CH2:25][CH3:26])[CH3:24])[C:6]3=[O:22])[CH2:14][CH2:15][C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)[CH2:79][C:80]3[CH:85]=[C:84]([F:86])[CH:83]=[C:82]([F:87])[CH:81]=3)[CH2:75][C:74]3[C:69](=[CH:70][CH:71]=[CH:72][CH:73]=3)[CH2:68]2)=[CH:90][CH:91]=1

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 59746631HCID 59746631, compoundHCID 67270863(S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-4-phenylbutanoic acid

Product 1

HCID 67272294HCID 67272294, compoundYield 92.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-4-phenylbutanoic acid (Preparation B, 25 mg, 0.069 mmol) in dichloromethane (1 mL) was added Hunig's base (27 mg, 0.21 mmol) to make a clear solution and HATU (34 mg, 0.090 mmol) was then added. After stirring for 1 h, to the reaction mixture was added (1S,2S)-1-((R)-2-(4-methoxybenzyl)-1,2,3,4-tetrahydroisoquinolin-3-yl)-2-amino-3-(3,5-difluorophenyl)propan-1-ol (Preparation A, 33.5 mg, 0.076 mmol) and the reaction mixture was stirred at rt overnight. Solvent was removed and the crude mixture was purified by silica gel Flash Chromatography to give 50 mg of the title compound: 1H NMR (CD3OD, 500 MHz) δ 0.68 (3H, d, J=5 Hz), 0.94-1.08 (4H, m), 1.61-1.66 (2H, m), 1.94 (3H, s), 2.01-2.20 (4H, m), 2.46 (1H, m), 2.60-2.69 (2H, m), 2.76-2.94 (2H, m), 3.00 (1H, m), 3.07 (1H, dd, J=5, 15 Hz), 3.22 (1H, m), 3.46 (1H, dt, J=5, 10 Hz), 3.62-3.69 (3H, m), 3.74 (3H, s), 3.82 (1H, m), 4.02 (1H, d, J=15 Hz), 4.14 (1H, dd, J=5, 10 Hz), 4.72 (1H, m), 6.70 (1H, m), 6.81 (2H, d, J=10 Hz), 6.87 (2H, d, J=10 Hz), 6.96 (1H, d, J=5 Hz), 7.08-7.13 (6H, m), 7.17-7.20 (2H, m), 7.24 (2H, d, J=5 Hz). MS (ESI)(M+H)+ 781.39.

Workup

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

Sources & evidence

ORD record
ord-50b2c1da0d8844e8a44e0db7f9ce3f49
Source dataset
uspto-grants-2011_03
Patent number
US07902218B2

Reaction notes

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