Ethylenediamine → HCID 86608457, compound

HRID 2109812Notes

Reaction equation

HRID 2109812 reaction equation
C(OC(=O)[NH:7][CH2:8][CH2:9][C:10]([NH:12][CH2:13][CH2:14][C:15]([NH:17][CH2:18][CH2:19][CH2:20][N:21]([C@H:34]1[CH2:58][CH2:57][C@@:56]2([CH3:59])[C:36](=[CH:37][CH2:38][C@@H:39]3[C@@H:55]2[CH2:54][CH2:53][C@@:52]2([CH3:60])[C@H:40]3[CH2:41][CH2:42][C@@H:43]2[C@H:44]([CH3:51])[CH2:45][CH2:46][CH2:47][CH:48]([CH3:50])[CH3:49])[CH2:35]1)[S:22]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[N+:31]([O-:33])=[O:32])(=[O:24])=[O:23])=[O:16])=[O:11])(C)(C)C.F[C:63](F)(F)[C:64]([OH:66])=O.[OH-].[Na+].C1(=O)N(OC(=O)C[CH2:79][CH2:80][CH2:81][CH2:82][NH:83][C:84]2[CH:89]=[CH:88][C:87]([N+:90]([O-:92])=[O:91])=[CH:86][C:85]=2[N+:93]([O-:95])=[O:94])C(=O)CC1.C(N(C(C)C)CC)(C)C.C(N)CN>C(Cl)Cl.CO.C(Cl)Cl>[CH3:50][CH:48]([CH2:47][CH2:46][CH2:45][C@H:44]([C@@H:43]1[C@:52]2([CH3:60])[C@H:40]([C@H:39]3[C@H:55]([CH2:54][CH2:53]2)[C@:56]2([CH3:59])[C:36]([CH2:35][C@@H:34]([N:21]([S:22]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=4[N+:31]([O-:33])=[O:32])(=[O:23])=[O:24])[CH2:20][CH2:19][CH2:18][NH:17][C:15](=[O:16])[CH2:14][CH2:13][NH:12][C:10](=[O:11])[CH2:9][CH2:8][NH:7][C:64](=[O:66])[CH2:63][CH2:79][CH2:80][CH2:81][CH2:82][NH:83][C:84]4[CH:89]=[CH:88][C:87]([N+:90]([O-:92])=[O:91])=[CH:86][C:85]=4[N+:93]([O-:95])=[O:94])[CH2:58][CH2:57]2)=[CH:37][CH2:38]3)[CH2:41][CH2:42]1)[CH3:51])[CH3:49]

Participants

9

Reactant 6

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 162171391-{[6-(2,4-Dinitroanilino)hexanoyl]oxy}pyrrolidine-2,5-dioneHCID 67199379HCID 67199379, compound

Product 1

HCID 86608457HCID 86608457, compoundYield 96%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

tert-butyl 3-({3-[(3-{(3β)-cholest-5-en-3-yl[(2-nitrophenyl)sulfonyl]amino}propyl)amino]-3-oxopropyl}amino)-3-oxopropylcarbamate (18, 52 mg, 0.060 mmol) was treated with trifluoroacetic acid in CH2Cl2 (2:25, 10 mL). After 1 h at 23° C., TLC analysis (MeOH/CH2Cl2, 1:25) revealed conversion to the more polar primary amine. Aqueous NaOH (1 M, 40 mL) was added, the mixture was extracted with CH2Cl2 (2×10 mL), the organic layers were dried over anhydrous Na2SO4, and the solvent was removed in vacuo. The remaining residue was dissolved in CH2Cl2 (10 mL) and 6-(2,4-dinitrophenyl)aminohexanoic acid succinimidyl ester (71 mg, 0.180 mmol) and diisopropylethylamine (50 μL, 0.287 mmol) were added. After 8 h at 23° C., ethylenediamine (50 μL) was added with stirring for 30 min to consume the excess active ester. CH2Cl2 (5 mL) and aqueous citric acid (10%, 25 mL) were added followed by extraction with CH2Cl2 (2×5 mL). The organic layer was dried over anhydrous Na2SO4 and removed in vacuo. Flash column chromatography (MeOH/CH2Cl2, 1:25) afforded 21 (60 mg, 96%), mp 106-108° C.; 1H NMR (500 MHz, CDCl3) δ 9.10 (d, J=2.59 Hz, 1H), 8.57 (t, J=4.98 Hz, 1H), 8.25 (dd, J=2.6 Hz, J=9.5 Hz, 1H), 8.01-7.97 (m, 1H), 7.74-7.68 (m, 2H), 7.64-7.59 (m, 1H), 6.93 (d, J=9.6 Hz, 1H), 6.70 (t, J=5.5 Hz, 1H), 6.65 (t, J=5.7 Hz, 1H), 6.58 (d, J=5.1 Hz, 1H), 5.19 (d, J=4.9 Hz, 1H), 3.57-3.51 (m, 5H), 3.44-3.34 (m, 6H), 2.43 (t, J=5.9 Hz, 2H), 2.38 (t, J=5.9 Hz, 2H), 2.21 (d, J=7.4 Hz, 2H), 2.01-1.67 (m, 13H), 1.58-1.22 (m, 14H), 1.18-0.97 (m, 9H), 0.94 (s, 3H), 0.90 (d, J=6.5 Hz, 3H), 0.87 (d, J=2.4 Hz, 3H), 0.86 (d, J=2.2 Hz, 3H), 0.66 (s, 3H); 13C NMR (125.8 MHz, CDCl3) δ 172.9 172.1 (×2), 148.6, 148.1, 140.0, 136.1, 133.9, 133.8, 131.9, 130.8, 130.5, 130.4, 124.5, 124.3, 122.7, 114.2, 59.3, 56.8, 56.3, 50.2, 43.5, 42.5, 41.8, 39.8, 39.7, 38.4, 37.8, 36.7, 36.4, 36.4, 36.3, 35.9, 35.9, 35.8, 34.1, 32.0, 31.9, 28.6, 28.4, 28.2, 27.7, 26.6, 25.8, 25.2, 25.1, 24.4, 24.0, 23.0, 22.7, 21.1, 19.6, 18.9, 12.0; IR (film) νmax 3378, 3287, 2937, 2867, 1634, 1622, 1548, 1337 cm−1; CI m/z 1049.5764 (MH+, C54H81N8O11S requires 1049.5745).

Workup

  1. extractionthe mixture was extracted with CH2Cl2 (2×10 mL)
  2. dry with materialthe organic layers were dried over anhydrous Na2SO4
  3. customthe solvent was removed in vacuo
  4. dissolutionThe remaining residue was dissolved in CH2Cl2 (10 mL)
  5. waitAfter 8 h at 23° C.
  6. customto consume the excess active ester
  7. additionCH2Cl2 (5 mL) and aqueous citric acid (10%, 25 mL) were added
  8. extractionfollowed by extraction with CH2Cl2 (2×5 mL)
  9. dry with materialThe organic layer was dried over anhydrous Na2SO4
  10. customremoved in vacuo

Sources & evidence

ORD record
ord-c167dd0b44f840cb8d05f0ced24d23ba
Source dataset
uspto-grants-2009_04
Patent number
US07514400B2

Reaction notes

Loading…