1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 87524929, compound

HRID 2356304Notes

Reaction equation

HRID 2356304 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([C:78]2[CH:83]=[CH:82][C:81]([O:84][CH3:85])=[CH:80][CH:79]=2)([C:72]2[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=2)[O:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]([N:18]2[C:29]3[C:21](=[C:22]4[C:26](=[CH:27][CH:28]=3)[NH:25][CH:24]([C:30]([N:32]3[C:43]5[C:35](=[C:36]6[C:40](=[CH:41][CH:42]=5)[NH:39][CH:38]([C:44](N5C7C(=C8C(=CC=7)NC(C(OCCC7C=CC([N+]([O-])=O)=CC=7)=O)C8)C=C5)=[O:45])[CH2:37]6)[CH:34]=[CH:33]3)=[O:31])[CH2:23]4)[CH:20]=[CH:19]2)=[O:17])=[CH:5][CH:4]=1.[CH2:86]1[CH2:96][CH2:95][N:94]2[C:89](=[N:90][CH2:91][CH2:92][CH2:93]2)[CH2:88][CH2:87]1.[CH:97](N(C(C)C)CC)(C)C.FC(F)(F)[C:108]([O:110][C:111]1[C:116]([F:117])=[C:115]([F:118])[C:114]([F:119])=[C:113]([F:120])[C:112]=1[F:121])=[O:109]>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]([C:78]2[CH:79]=[CH:80][C:81]([O:84][CH3:85])=[CH:82][CH:83]=2)([C:72]2[CH:73]=[CH:74][CH:75]=[CH:76][CH:77]=2)[O:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]([N:18]2[C:29]3[C:21](=[C:22]4[C:26](=[CH:27][CH:28]=3)[NH:25][CH:24]([C:30]([N:32]3[C:43]5[C:35](=[C:36]6[C:40](=[CH:41][CH:42]=5)[NH:39][CH:38]([C:44]([N:94]5[C:93]7[C:86](=[C:87]8[C:97](=[CH:91][CH:92]=7)[NH:90][CH:89]([C:108]([O:110][C:111]7[C:112]([F:121])=[C:113]([F:120])[C:114]([F:119])=[C:115]([F:118])[C:116]=7[F:117])=[O:109])[CH2:88]8)[CH:96]=[CH:95]5)=[O:45])[CH2:37]6)[CH:34]=[CH:33]3)=[O:31])[CH2:23]4)[CH:20]=[CH:19]2)=[O:17])=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 81531DiisopropylethylamineHCID 4327891Pentafluorophenyl TrifluoroacetateHCID 87525231HCID 87525231, compound

Product 1

HCID 87524929HCID 87524929, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Nitrophenylethyl ester 18 (1.39 g, 1.22 mol) was deprotected by treatment with 6.6 mmol of DBU in 20 mL of anhydrous DMF for 2 h at 50° C. DMF was evaporated and the residue triturated with methanol. Insoluble material was collected by filtration washed with methanol and dried under vacuum overnight. The solid was re-dissolved in 20 mL of DMF and treated with diisopropylethylamine (1.5 mL, 8.6 mmol) and pentafluorophenyl trifluoroacetate (1.0 mL, 5.8 mmol). After being stirred at room temperature for 2 h DMF was evaporated and the residue triturated with methanol. Precipitated product was collected by filtration, washed with methanol and dried under vacuum to afford 1.41 g (100%) of the desired PFP ester 19 as a yellow solid. 1H NMR (DMSO-d6) δ 12.54 (s, 1H), 11.80 (s, 1H), 11.70 (s, 1H), 8.43 (d, J=9 Hz, 1H), 8.30 (m, 1H), 8.22 (d, J=9 Hz, 1H), 7.558 (s, 1H), 7.5-7.2 (m, 12H), 7.09 (s, 1H), 6.97 (s, 1H), 6.87 (d, J=9 Hz, 4H), 4.6 (m, 4H), 4.11 (t, J=7 Hz, 2H), 3.73 (s, 6H), 3.43 (m, 4H), 3.28 (t, J=8 Hz, 2H), 2.97 (t, J=6 Hz, 2H), 2.37 (t, J=6 Hz, 2H), 1.57 (m, 4H), 1.40 (m, 2H).

Workup

  1. customDMF was evaporated
  2. customthe residue triturated with methanol
  3. filtrationInsoluble material was collected by filtration
  4. washwashed with methanol
  5. customdried under vacuum overnight
  6. dissolutionThe solid was re-dissolved in 20 mL of DMF
  7. customwas evaporated
  8. customthe residue triturated with methanol
  9. filtrationPrecipitated product was collected by filtration
  10. washwashed with methanol
  11. customdried under vacuum

Sources & evidence

ORD record
ord-ab1366e9f04248cf959e0dc5a4bd5ce7
Source dataset
uspto-grants-2010_07
Patent number
US07759126B2

Reaction notes

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