5-(2-Oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanoic acid → {3-Benzyloxy-4-[5-(2-oxo-hexahydro-thieno[3,4-d]imidazol-4-yl)-pentanoylamino]-phenyl}-carbamic acid 9H-fluoren-9-ylmethyl ester

HRID 1354849Notes

Reaction equation

HRID 1354849 reaction equation
[O:1]=[C:2]1[NH:6][CH:5]2[CH2:7][S:8][CH:9]([CH2:10][CH2:11][CH2:12][CH2:13][C:14]([OH:16])=O)[CH:4]2[NH:3]1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C.[CH:50]1[C:62]2[CH:61]([CH2:63][O:64][C:65](=[O:82])[NH:66][C:67]3[CH:72]=[CH:71][C:70]([NH2:73])=[C:69]([O:74][CH2:75][C:76]4[CH:81]=[CH:80][CH:79]=[CH:78][CH:77]=4)[CH:68]=3)[C:60]3[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=3)[C:54]=2[CH:53]=[CH:52][CH:51]=1>CC(N(C)C)=O>[CH:50]1[C:62]2[CH:61]([CH2:63][O:64][C:65](=[O:82])[NH:66][C:67]3[CH:72]=[CH:71][C:70]([NH:73][C:14](=[O:16])[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]4[CH:4]5[CH:5]([NH:6][C:2](=[O:1])[NH:3]5)[CH2:7][S:8]4)=[C:69]([O:74][CH2:75][C:76]4[CH:77]=[CH:78][CH:79]=[CH:80][CH:81]=4)[CH:68]=3)[C:60]3[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=3)[C:54]=2[CH:53]=[CH:52][CH:51]=1

Participants

6

Reactant 4

HCID 2535-(2-Oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanoic acidHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58865047(4-Amino-3-benzyloxyphenyl)-carbamic acid 9H-fluoren-9-ylmethyl ester

Product 1

HCID 72447686{3-Benzyloxy-4-[5-(2-oxo-hexahydro-thieno[3,4-d]imidazol-4-yl)-pentanoylamino]-phenyl}-carbamic acid 9H-fluoren-9-ylmethyl esterYield 73.7%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

5-(2-Oxo-hexahydro-thieno[3,4-d]imidazol-4-yl)-pentanoic acid (388) (0.293 g, 1.2 mmol) and 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyl-uronium hexafluorophosphate (HBTU) (0.455 g, 1.2 mmol) were combined and dissolved in DMA (24 mL). iPr2EtN (0.313 mL, 1.8 mmol) was added and the mixture was shaken for 30 minutes at room temperature. The (4-amino-3-benzyloxy-phenyl)-carbamic acid 9H-fluoren-9-ylmethyl ester (65) (0.25 g, 0.573 mmol) was added and the mixture was shaken in a 40 mL I-Chem vial for 16 h. LC-MS indicated complete coupling at this point. The mixture was poured into ice-water and a very pale/purple powder precipitated. Collection by filtration under reduced pressure followed by drying under high vacuum for 16 h gave the desired product (389) as a white/purple solid (0.28 g, 0.422 mmol, 73.7% yield). LC-MS (ESI): (exact mass: 662.26) m/e 663.2 [M+1]+ (100%).

Workup

  1. stirringthe mixture was shaken in a 40 mL I-Chem vial for 16 h
  2. customa very pale/purple powder precipitated
  3. customCollection
  4. filtrationby filtration under reduced pressure
  5. customby drying under high vacuum for 16 h

Sources & evidence

ORD record
ord-1b4ad6fd82d346d38da330674ef87e47
Source dataset
uspto-grants-2007_05
Patent number
US07223759B2

Reaction notes

Loading…