HCID 178471816, compound → HCID 178471198, compound

HRID 406170Notes

Reaction equation

HRID 406170 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:49][CH3:50])=[O:48])[C:20](=[O:27])[C:19]1[C:10](=[CH:11][C:12]2[C:13](=[O:43])[C:14]([NH:30][C@@H: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](=[NH:29])[C:17]=2[C:18]=1[OH:28])[C:9]3=[O:44].[Br-].[CH2:52]([O:54][C:55](=[O:59])[CH2:56][CH2:57][Zn+])[CH3:53]>C1COCC1>[CH2:52]([O:54][C:55](=[O:59])[CH2:56][CH2:57][C:13]1([OH:43])[C:12]2[CH:11]=[C:10]3[C:19]([C:20](=[O:27])[C@@:21]4([O:25][CH3:26])[C@@:8]([OH:45])([C:9]3=[O:44])[C:7]3[C:2]([OH:1])=[C:3]([C:47]([O:49][CH3:50])=[O:48])[C:4]([CH3:46])=[CH:5][C:6]=3[CH2:23][C@H:22]4[OH:24])=[C:18]([OH:28])[C:17]=2[C:16](=[NH:29])[CH:15]=[C:14]1[NH:30][C@@H:31]1[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]1)[CH3:53]

Participants

4

Reactant 2

HCID 178471816HCID 178471816, compoundHCID 178497453HCID 178497453, compound

Product 1

HCID 178471198HCID 178471198, compoundYield 12%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a −78° C. solution of (6R,6aS,14aR)-methyl 1,6,8,14a-tetrahydroxy-11-((2S,3R,4R,5R,6S)-4-hydroxy-3,5-dimethoxy-6-methyltetrahydro-2H-pyran-2-ylamino)-9-imino-6a-methoxy-3-methyl-7,12,14-trioxo-5,6,6a,7,9,12,14,14a-octahydrobenzo[a]tetracene-2-carboxylate (50 mg, 0.072 mmol) in THF (2 mL) was added a solution of 3-ethoxy-3-oxopropylzinc bromide in THF (0.5 M, 1.15 mL, 0.58 mmol) dropwise. The reaction mixture was stirred at −78° C. for 2 h, and then quenched with a saturated solution of ammonium chloride. The mixture was extracted with chloroform (3×10 mL). The combined organics were dried (Na2SO4), filtered and concentrated. The crude was purified by preparative TLC (silica gel, 85:15 chloroform/methanol) to afford (6R,6aS,14aR)-methyl 12-(3-ethoxy-3-oxopropyl)-1,6,8,12,14a-pentahydroxy-11-((2S,3R,4R,5R,6S)-4-hydroxy-3,5-dimethoxy-6-methyltetrahydro-2H-pyran-2-ylamino)-9-imino-6a-methoxy-3-methyl-7,14-dioxo-5,6,6a,7,9,12,14,14a-octahydrobenzo[a]tetracene-2-carboxylate (7 mg, 12%) as an orange solid and as a mixture of diastereomers: 1H NMR (500 MHz, CD3OD) δ 7.18 (s, 1H), 6.57 (s, 1H), 5.54 (s, 1H), 4.96 (s, 1H), 4.88-4.83 (m, 2H), 3.84 (s, 3H), 3.76 (s, 3H), 3.75-3.66 (m, 3H), 3.57 (s, 3H), 3.34 (s, 3H), 3.25-3.16 (m, 2H), 3.03 (t, J=9.0 Hz, 1H), 2.39 (s, 3H), 2.15-1.85 (m, 4H), 1.45-1.26 (m, 1H), 1.25 (d, J=5.5 Hz, 3H), 1.09 (t, J=7.0 Hz, 3H); MS (ESI+) m/z 799 (M+H); HPLC >99% (AUC), tR 10.04 min.

Workup

  1. customquenched with a saturated solution of ammonium chloride
  2. extractionThe mixture was extracted with chloroform (3×10 mL)
  3. dry with materialThe combined organics were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude was purified by preparative TLC (silica gel, 85:15 chloroform/methanol)

Sources & evidence

ORD record
ord-7eb5599b8f384892b1c50ed7395c23c0
Source dataset
uspto-grants-2014_06
Patent number
US08754054B2

Reaction notes

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