Diisopropylethylamine → {(3S,5S)-1-{(S)-2-[(S)-2-(tert-Butoxycarbonyl-methyl-amino)-propionylamino]-2-cyclohexyl-acetyl}-5-[(R)-(1,2,3,4-tetrahydro-naphthalen-1-yl)carbamoyl]-pyrrolidin-3-yl}-carbamic acid 9H-fluoren-9-ylmethyl ester

HRID 1481914Notes

Reaction equation

HRID 1481914 reaction equation
[N:1]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])([CH3:7])[C@H:2]([C:4]([OH:6])=O)[CH3:3].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH:48]1[C:60]2[CH:59]([CH2:61][O:62][C:63](=[O:93])[NH:64][C@H:65]3[CH2:69][C@@H:68]([C:70](=[O:82])[NH:71][C@H:72]4[C:81]5[C:76](=[CH:77][CH:78]=[CH:79][CH:80]=5)[CH2:75][CH2:74][CH2:73]4)[N:67]([C:83](=[O:92])[C@@H:84]([NH2:91])[CH:85]4[CH2:90][CH2:89][CH2:88][CH2:87][CH2:86]4)[CH2:66]3)[C:58]3[C:53](=[CH:54][CH:55]=[CH:56][CH:57]=3)[C:52]=2[CH:51]=[CH:50][CH:49]=1>CN(C=O)C.C(OCC)(=O)C>[CH:48]1[C:60]2[CH:59]([CH2:61][O:62][C:63](=[O:93])[NH:64][C@H:65]3[CH2:69][C@@H:68]([C:70](=[O:82])[NH:71][C@H:72]4[C:81]5[C:76](=[CH:77][CH:78]=[CH:79][CH:80]=5)[CH2:75][CH2:74][CH2:73]4)[N:67]([C:83](=[O:92])[C@@H:84]([NH:91][C:4](=[O:6])[C@@H:2]([N:1]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH3:7])[CH3:3])[CH:85]4[CH2:90][CH2:89][CH2:88][CH2:87][CH2:86]4)[CH2:66]3)[C:58]3[C:53](=[CH:54][CH:55]=[CH:56][CH:57]=3)[C:52]=2[CH:51]=[CH:50][CH:49]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 7009590(2S)-2-(((tert-butoxy)carbonyl)(methyl)amino)propanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 118677380{(3S,5S)-1-((S)-2-amino-2-cyclohexyl-acetyl)-5-[(R)-(1,2,3,4-tetrahydro-naphthalen-1-yl)carbamoyl]-pyrrolidin-3-yl}-carbamic acid 9H-fluoren-9-ylmethyl ester2×

Product 1

HCID 90220982{(3S,5S)-1-{(S)-2-[(S)-2-(tert-Butoxycarbonyl-methyl-amino)-propionylamino]-2-cyclohexyl-acetyl}-5-[(R)-(1,2,3,4-tetrahydro-naphthalen-1-yl)carbamoyl]-pyrrolidin-3-yl}-carbamic acid 9H-fluoren-9-ylmethyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of Boc-N-Me-Ala-OH (2.55 g, 12.57 mmol) in DMF (30 mL) were added HATU (4.78 g, 12.57 mmol) and DIPEA (9.9 mL, 57.16 mmol). After 30 min, the mixture was cooled to 0° C. and {(3S,5S)-1-((S)-2-amino-2-cyclohexyl-acetyl)-5-[(R)-(1,2,3,4-tetrahydro-naphthalen-1-yl)carbamoyl]-pyrrolidin-3-yl}-carbamic acid 9H-fluoren-9-ylmethyl ester (Intermediate 24) (7.5 g, 11.43 mmol) in DMF (50 mL) and the cooling bath removed. After 4 h the mixture was diluted with ethyl acetate, washed with water, dried over sodium sulfate and concentrated. The residue was purified by silica gel chromatography to afford the title compound as an off white solid (5.32 g) LC-MS: 806 (M+H).

Workup

  1. washwashed with water
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated
  4. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-7436cab788b74d768e44b9ad011b6e48
Source dataset
uspto-grants-2016_08
Patent number
US09409888B2

Reaction notes

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