Pyrrolidine → HCID 67121343, compound

HRID 406148Notes

Reaction equation

HRID 406148 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.[NH:61]1[CH2:65][CH2:64][CH2:63][CH2:62]1>C1COCC1>[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:61]1[CH2:65][CH2:64][CH2:63][CH2:62]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

5

Reactant 3

HCID 31268PyrrolidineHCID 27960291-Hydroxybenzotriazole hydrateHCID 67121425HCID 67121425, compound

Product 1

HCID 67121343HCID 67121343, compoundYield 2.8%

Reagents, catalysts & solvents 1

HCID 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 (56 mg, 0.082 mmol) in THF (2 mL) was added polystyrene carbodiimide (0.15 mg, 0.17 mmol) and 1-hydroxybenzotriazole hydrate (22 mg, 0.16 mmol), and then the reaction mixture was stirred at room temperature under nitrogen. After 15 min, pyrrolidine (11 mg, 0.16 mmol) was added and the reaction mixture was stirred at room temperature under nitrogen. After 5 h, the reaction mixture was filtered and concentrated under reduced pressure. The crude material was purified by preparative HPLC (10:90 acetonitrile/water to 60:40 acetonitrile/water with 0.05% TFA over 10 min, then isocratic). The resulting product was lyophilized from acetonitrile (3 mL) and water (1 mL) to give (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-(pyrrolidine-1-carbonyl)-6,6a-dihydrobenzo[a]tetracene-7,9,12,14(5H,14aH)-tetraone (1.7 mg, 2.8%) as a mixture of diastereomers and as a dark red solid: 1H NMR (500 MHz, CD3OD) δ 8.10 (s, 1H), 6.64 (s, 1H), 6.17 (s, 0.3H), 6.01 (s, 0.7H), 4.96-4.87 (m, 2H), 3.74 (s, 3H), 3.64 (s, 1H), 3.57 (s, 3H), 3.52 (d, J=18.0 Hz, 3H), 3.46-3.39 (m, 6H), 3.26-3.20 (m, 1H), 3.08-3.02 (m, 2H), 2.08 (s, 3H), 1.93-1.87 (m, 4H), 1.28 (d, J=6.0 Hz, 2.1H), 1.22 (d, J=6.0 Hz, 0.9H); MS (ESI+) m/z 737 (M+H); HPLC 94.4% (AUC), tR 10.71 min.

Workup

  1. stirringthe reaction mixture was stirred at room temperature under nitrogen
  2. waitAfter 5 h
  3. filtrationthe reaction mixture was filtered
  4. concentrationconcentrated under reduced pressure
  5. customThe crude material was purified by preparative HPLC (10:90 acetonitrile/water to 60:40 acetonitrile/water with 0.05% TFA over 10 min

Sources & evidence

ORD record
ord-d547539952044d40afd1a0d75303770e
Source dataset
uspto-grants-2014_06
Patent number
US08754054B2

Reaction notes

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