Hydrochloric Acid → HCID 67121415, compound

HRID 406142Notes

Reaction equation

HRID 406142 reaction equation
[OH:1][C:2]1[C:7]2[C@@:8]3([OH:45])[C@@:21]([O:25][CH3:26])([C@H:22]([OH:24])[CH2:23][C:6]=2[CH:5]=[C:4]([CH3:46])[C:3]=1[C:47](O)=[O:48])[C:20](=[O:27])[C:19]1[C:10](=[CH:11][C:12]2[C:13](=[O:43])[C:14]([NH:30][CH:31]4[C@H:36]([O:37][CH3:38])[C@H:35]([OH:39])[C@@H:34]([O:40][CH3:41])[C@H:33]([CH3:42])[O:32]4)=[CH:15][C:16](=[O:29])[C:17]=2[C:18]=1[OH:28])[C:9]3=[O:44].O.ON1C2C=CC=CC=2N=N1.[C:61]1([N:67]2[CH2:72][CH2:71][NH:70][CH2:69][CH2:68]2)[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1.[ClH:73]>C1COCC1.CO>[ClH:73].[OH:1][C:2]1[C:7]2[C@@:8]3([OH:45])[C@@:21]([O:25][CH3:26])([C@H:22]([OH:24])[CH2:23][C:6]=2[CH:5]=[C:4]([CH3:46])[C:3]=1[C:47]([N:70]1[CH2:71][CH2:72][N:67]([C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=2)[CH2:68][CH2:69]1)=[O:48])[C:20](=[O:27])[C:19]1[C:10](=[CH:11][C:12]2[C:13](=[O:43])[C:14]([NH:30][CH:31]4[C@H:36]([O:37][CH3:38])[C@H:35]([OH:39])[C@@H:34]([O:40][CH3:41])[C@H:33]([CH3:42])[O:32]4)=[CH:15][C:16](=[O:29])[C:17]=2[C:18]=1[OH:28])[C:9]3=[O:44]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 70961-PhenylpiperazineHCID 27960291-Hydroxybenzotriazole hydrateHCID 67121425HCID 67121425, compound

Product 1

HCID 67121415HCID 67121415, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (6R,6aS,14aR)-1,6,8,14a-tetrahydroxy-11-((3R,4R,5R,6S)-4-hydroxy-3,5-dimethoxy-6-methyltetrahydro-2H-pyran-2-ylamino)-6a-methoxy-3-methyl-7,9,12,14-tetraoxo-5,6,6a,7,9,12,14,14a-octahydrobenzo[a]tetracene-2-carboxylic acid (60 mg, 0.09 mmol) in THF (2 mL) was added polystyrene-carbodiimide (156 mg, 0.18 mmol), 1-hydroxybenzotriazole hydrate (24 mg, 0.18 mmol) and 1-phenylpiperazine (21 mg, 0.13 mmol). The reaction mixture was stirred at room temperature under nitrogen for 5 h. The reaction was filtered through a micro filter and concentrated. The crude material was purified by preparative TLC (silica gel, 90:10 dichloromethane/methanol) to afford a dark red solid. The solid was dissolved in methanol (1 mL) and treated with HCl (1.25 M solution in methanol, 0.5 mL) at 0° C. The solution was concentrated and triturated with diethyl ether to afford (6R,6aS,14aR)-1,6,8,14a-tetrahydroxy-11-((3R,4R,5R,6S)-4-hydroxy-3,5-dimethoxy-6-methyltetrahydro-2H-pyran-2-ylamino)-6a-methoxy-3-methyl-2-(4-phenylpiperazine-1-carbonyl)-6,6a-dihydrobenzo[a]tetracene-7,9,12,14(5H,14aH)-tetraone hydrochloride as a mixture of diastereomers (9.0 mg, 25%) and as a red solid: 1H NMR (500 MHz, CD3OD) δ 8.10 (s, 1H), 7.60-7.20 (m, 5H), 6.70 (s, 1H), 6.20-6.10 (m, 0.3H), 6.04-5.95 (m, 0.7H), 5.49 (s, 1H), 4.96-4.85 (m, 1H), 4.18-4.08 (m, 1H), 4.05-3.89 (m, 1H), 3.78-3.62 (m, 7H), 3.54 (s, 3H), 3.61-3.52 (m, 2H), 3.51-3.41 (m, 7H), 3.27-3.16 (m, 1H), 3.09-2.90 (m, 1H), 3.16 (s, 3H), 1.30-1.20 (m, 3H); MS (ESI−) m/z 826 (M−H); HPLC 94.2% (AUC), tR 11.89 min.

Workup

  1. filtrationThe reaction was filtered through
  2. filtrationa micro filter
  3. concentrationconcentrated
  4. customThe crude material was purified by preparative TLC (silica gel, 90:10 dichloromethane/methanol)
  5. customto afford a dark red solid
  6. concentrationThe solution was concentrated
  7. customtriturated with diethyl ether

Sources & evidence

ORD record
ord-cdacd5c217ad4faea9b658967bfb9401
Source dataset
uspto-grants-2014_06
Patent number
US08754054B2

Reaction notes

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