HCID 178453758, compound → HCID 178511412, compound

HRID 530146Notes

Reaction equation

HRID 530146 reaction equation
[NH2:1][C:2]1[N:11]=[C:10]([OH:12])[C:9]2[C:4](=[N:5][CH:6]=[C:7]([CH2:13][NH:14][C:15]3[CH:55]=[CH:54][C:18]([C:19]([NH:21][C@H:22]([C:47]([O:49]C(C)(C)C)=[O:48])[CH2:23][CH2:24][C:25](=[O:46])[NH:26][CH2:27][CH2:28][O:29][CH2:30][CH2:31][O:32][CH2:33][CH2:34][O:35][CH2:36][CH2:37][NH:38]C(=O)OC(C)(C)C)=[O:20])=[CH:17][CH:16]=3)[N:8]=2)[N:3]=1>Cl>[NH2:38][CH2:37][CH2:36][O:35][CH2:34][CH2:33][O:32][CH2:31][CH2:30][O:29][CH2:28][CH2:27][NH:26][C:25](=[O:46])[CH2:24][CH2:23][C@H:22]([NH:21][C:19](=[O:20])[C:18]1[CH:54]=[CH:55][C:15]([NH:14][CH2:13][C:7]2[N:8]=[C:9]3[C:4](=[N:5][CH:6]=2)[N:3]=[C:2]([NH2:1])[N:11]=[C:10]3[OH:12])=[CH:16][CH:17]=1)[C:47]([OH:49])=[O:48]

Participants

3

Reactant 1

HCID 178453758HCID 178453758, compound

Product 1

HCID 178511412HCID 178511412, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent2×

Procedure

To (S)-tert-butyl 21-(4-((2-amino-4-hydroxypteridin-6-yl)methylamino)benzamido)-2,2-dimethyl-4,18-dioxo-3,8,11,14-tetraoxa-5,17-diazadocosan-22-oate (425 mg, 0.551 mmol) aqueous 6 M hydrochloric acid (10 mL) was added. The reaction was stirred at ambient temperature for 16 hours. After this time, the reaction was not complete. The reaction was concentrated under reduced pressure and dissolved in N,N-dimethylformamide (5 mL). To the resulting mixture TFA (7 mL) was added and reaction mixture stirred at ambient temperature for 16 hours. After this time, the reaction was diluted with 6 M aqueous hydrochloric acid (50 mL) and filtered through diatomaceous earth. The filter cake was rinsed with methanol (40 mL), and the filtrate obtained was concentrated under reduced pressure. The residue obtained was purified by semi-preparative HPLC (100:0 to 3:7 H2O/CH3CN with 0.05% TFA over 25 min). Further purification by semi-preparative HPLC (100:0 to 3:7 H2O/CH3CN with 0.05% TFA over 25 min) was required to obtain pure (S)-1-amino-16-(4-((2-amino-4-hydroxypteridin-6-yl)methylamino)benzamido)-13-oxo-3,6,9-trioxa-12-azaheptadecan-17-oic acid (121 mg, 36%) as a yellow solid that was obtained via lyophilization: 1H NMR (300 MHz, DMSO-d6) δ 10.88 (vbs, 1H), 8.65 (s, 1H), 8.20 (d, J=6.6 Hz, 1H), 7.95-7.89 (m, 1H), 7.78 (bs, 2H), 7.65 (d, J=8.7 Hz, 2H), 7.00-6.90 (m, 2H), 6.64 (d, J=8.7 Hz, 2H), 4.49 (s, 2H), 4.31-4.28 (m, 1H), 3.78-3.45 (m, 12H), 3.43-3.35 (m, 2H), 3.28-3.20 (m, 2H), 3.02-2.98 (m, 2H), 2.23-2.17 (m, 2H), 2.12-2.00 (m, 1H), 1.99-1.87 (m, 1H); ESI MS m/z=614 [M−H]−.

Workup

  1. concentrationThe reaction was concentrated under reduced pressure
  2. dissolutiondissolved in N,N-dimethylformamide (5 mL)
  3. additionTo the resulting mixture TFA (7 mL) was added
  4. customreaction mixture
  5. stirringstirred at ambient temperature for 16 hours
  6. filtrationfiltered through diatomaceous earth
  7. washThe filter cake was rinsed with methanol (40 mL)
  8. customthe filtrate obtained
  9. concentrationwas concentrated under reduced pressure
  10. customThe residue obtained
  11. customwas purified by semi-preparative HPLC (100:0 to 3:7 H2O/CH3CN with 0.05% TFA over 25 min)
  12. customFurther purification by semi-preparative HPLC (100:0 to 3:7 H2O/CH3CN with 0.05% TFA over 25 min)

Sources & evidence

ORD record
ord-243bda7441bd47ffbcdd568a42962fc7
Source dataset
uspto-grants-2016_05
Patent number
US09352049B2

Reaction notes

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