4-Aminobenzoic Acid → HCID 131726467, compound

HRID 1354870Notes

Reaction equation

HRID 1354870 reaction equation
[NH:1]([C:33]([O:35][CH2:36][CH:37]=[CH2:38])=[O:34])[C@@H:2]([C:4]([NH:6][C@H:7]([C:15]([NH:17][C@H:18]([C:30]([OH:32])=[O:31])[CH2:19][CH2:20][CH2:21][CH2:22][NH:23][C:24]([O:26][CH2:27][CH:28]=[CH2:29])=[O:25])=[O:16])[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:5])[CH3:3].[CH3:39][C:40]([NH:51][CH2:52][CH:53]([OH:69])[CH2:54][O:55][C:56]1[C:61]2[C:62]3[C:67]([NH:68][C:60]=2[CH:59]=[CH:58][CH:57]=1)=[CH:66][CH:65]=[CH:64][CH:63]=3)([C:42]1[CH:47]=[CH:46][C:45]([N:48]=[N+:49]=[N-:50])=[CH:44][CH:43]=1)[CH3:41].[CH:70]1[C:75]([C:76]([OH:78])=[O:77])=[CH:74][CH:73]=[C:72]([NH2:79])[CH:71]=1.C(N(C(C)C)CC)(C)C.ON1C2C=CC=CC=2N=N1>CN(C)C=O.CC(O)C.CCOC(C)=O>[NH:1]([C:33]([O:35][CH2:36][CH:37]=[CH2:38])=[O:34])[C@@H:2]([C:4]([NH:6][C@H:7]([C:15]([NH:17][C@H:18]([C:30]([OH:32])=[O:31])[CH2:19][CH2:20][CH2:21][CH2:22][NH:23][C:24]([O:26][CH2:27][CH:28]=[CH2:29])=[O:25])=[O:16])[CH2:8][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)=[O:5])[CH3:3].[CH3:41][C:40]([NH:51][CH2:52][CH:53]([OH:69])[CH2:54][O:55][C:56]1[C:61]2[C:62]3[C:67]([NH:68][C:60]=2[CH:59]=[CH:58][CH:57]=1)=[CH:66][CH:65]=[CH:64][CH:63]=3)([C:42]1[CH:47]=[CH:46][C:45]([N:48]=[N+:49]=[N-:50])=[CH:44][CH:43]=1)[CH3:39].[CH:70]1[C:75]([C:76]([OH:78])=[O:77])=[CH:74][CH:73]=[C:72]([NH2:79])[CH:71]=1

Participants

7

Reactant 4

HCID 9784-Aminobenzoic AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 131726468HCID 131726468, compound

Product 1

HCID 131726467HCID 131726467, compoundYield 97%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 22055037Isopropanol ethyl acetateSolvent

Procedure

To a solution of 156 mg (194 μmol) of compound 16 and 26.3 mg (1.1 eq.) PABA in dry N,N-dimethyl formamide under an Argon atmosphere was added diisopropylethyl amine (34 μl, 1.0 eq.) and a catalytic amount of N-hydroxybenzotriazole (7.9 mg, 0.3 eq.). The reaction solution was stirred for 24 hours after which it was diluted with 10% propanol-2/EtOAc. The organic layer was washed with saturated sodium bicarbonate, 0.5 N potassium hydrogensulfate and brine, dried over anhydrous sodium sulfate and evaporated to dryness. The yellow residual film was purified by means of column chromatography (SiO2—CHCl3/MeOH 9/1) to yield 148 mg (97%) of the desired product 17. M.P. 196–197° C.; 1H-NMR (300 MHz, CDCl3): δ 1.20 (d, 3H, 3J=6.4 Hz, CH3-Ala), 1.27–2.05 (m, 6H, 3 CH2-Lys), 2.99 (dd, 1H, benzylic), 3.14 (m, 2H, N—CH2-Lys), 3.27 (dd, 1H, benzylic), 4.00–4.64 (m, 7H, 3 Hα and Aloc), 4.57 (s, 2H, benzylic-spacer), 5.14 (s, 2H, benzylic-spacer), 5.06–5.37 (m, 4H, Aloc), 5.72 (m, 1H, Aloc), 5.88 (m, 1H, Aloc), 7.10–7.46 (m, 11H, aromatic), 7.64 (d, 2H, 3J=8.3 Hz, aromatic) ppm; MS (FAB) m/e 809 (M+Na)+;; C41H50N6O10 (.½H2O) calculated C 61.87%; H, 6.46%; N, 10.56%; measured C, 61.84%; H, 6.38%; N, 10.38%.

Workup

  1. washThe organic layer was washed with saturated sodium bicarbonate, 0.5 N potassium hydrogensulfate and brine
  2. dry with materialdried over anhydrous sodium sulfate
  3. customevaporated to dryness
  4. customThe yellow residual film was purified by means of column chromatography (SiO2—CHCl3/MeOH 9/1)

Sources & evidence

ORD record
ord-b0841c85ba0d4769a77aad733ec2ed9c
Source dataset
uspto-grants-2007_05
Patent number
US07223837B2

Reaction notes

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