Diisopropylethylamine → {(3S,5S)-1-((S)-2-tert-butoxycarbonylamino-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 1481912Notes

Reaction equation

HRID 1481912 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].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.FC(F)(F)C(O)=O.[CH:59]1[C:71]2[CH:70]([CH2:72][O:73][C:74](=[O:94])[NH:75][C@H:76]3[CH2:80][C@@H:79]([C:81](=[O:93])[NH:82][C@H:83]4[C:92]5[C:87](=[CH:88][CH:89]=[CH:90][CH:91]=5)[CH2:86][CH2:85][CH2:84]4)[NH:78][CH2:77]3)[C:69]3[C:64](=[CH:65][CH:66]=[CH:67][CH:68]=3)[C:63]=2[CH:62]=[CH:61][CH:60]=1>CN(C=O)C>[CH:68]1[C:69]2[CH:70]([CH2:72][O:73][C:74](=[O:94])[NH:75][C@H:76]3[CH2:80][C@@H:79]([C:81](=[O:93])[NH:82][C@H:83]4[C:92]5[C:87](=[CH:88][CH:89]=[CH:90][CH:91]=5)[CH2:86][CH2:85][CH2:84]4)[N:78]([C:10](=[O:12])[C@@H:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH:13]4[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]4)[CH2:77]3)[C:71]3[C:63](=[CH:62][CH:61]=[CH:60][CH:59]=3)[C:64]=2[CH:65]=[CH:66][CH:67]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 7004938N-(tert-Butoxycarbonyl)-L-cyclohexylglycineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 90220816{(3S,5S)-5-[(R)-(1,2,3,4-Tetrahydro-naphthalen-1-yl)carbamoyl]-pyrrolidin-3-yl}-carbamic acid 9H-fluoren-9-ylmethyl ester trifluoroacetate2×

Product 1

HCID 90220880{(3S,5S)-1-((S)-2-tert-butoxycarbonylamino-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 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of (S)-tert-butoxycarbonylamino-cyclohexyl-acetic acid (Aldrich) (4.529 g, 17.622 mmol) in DMF (100 mL) were added HATU (6.7 g, 17.622 mmol) followed by DIPEA (13.87 mL, 80.101 mmol). The mixture was cooled to 0° C. and ({(3S,5S)-5-[(R)-(1,2,3,4-tetrahydro-naphthalen-1-yl)carbamoyl]-pyrrolidin-3-yl}-carbamic acid 9H-fluoren-9-ylmethyl ester trifluoroacetate (Intermediate 22) (9.5 g, 16.02 mmol) in DMF (50 mL) was added dropwise and then the cooling bath removed. After 4 h the mixture was diluted with ethyl acetate, washed with water, dried over sodium sulfate and concentrated to give the title compound as an off white solid (10 g) which was used without purification. LC-MS: 721 (M+H).

Workup

  1. customthe cooling bath removed
  2. additionAfter 4 h the mixture was diluted with ethyl acetate
  3. washwashed with water
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-21a17a61a9ef420086a2d45e0d3748bf
Source dataset
uspto-grants-2016_08
Patent number
US09409888B2

Reaction notes

Loading…