Potassium Carbonate → (6R,6aS,14aR)-methyl 6,8,14a-trihydroxy-11-((2S,3R,4R,5R,6S)-4-hydroxy-3,5-dimethoxy-6-methyltetrahydro-2H-pyran-2-ylamino)-6a-methoxy-3-methyl-7,9,12,14-tetraoxo-1-(2-oxo-2-(piperidin-1-yl)ethoxy)-5,6,6a,7,9,12,14,14a-octahydrobenzo[a]tetracene-2-carboxylate

HRID 406139Notes

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](=[O:29])[C:17]=2[C:18]=1[OH:28])[C:9]3=[O:44].C(=O)([O-])[O-].[K+].[K+].Br[CH2:58][C:59]([N:61]1[CH2:66][CH2:65][CH2:64][CH2:63][CH2:62]1)=[O:60]>>[OH:24][C@H:22]1[C@:21]2([O:25][CH3:26])[C@@:8]([OH:45])([C:9](=[O:44])[C:10]3[C:19]([C:20]2=[O:27])=[C:18]([OH:28])[C:17]2[C:16](=[O:29])[CH:15]=[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)[C:13](=[O:43])[C:12]=2[CH:11]=3)[C:7]2[C:2]([O:1][CH2:58][C:59](=[O:60])[N:61]3[CH2:66][CH2:65][CH2:64][CH2:63][CH2:62]3)=[C:3]([C:47]([O:49][CH3:50])=[O:48])[C:4]([CH3:46])=[CH:5][C:6]=2[CH2:23]1

Participants

Reactant 3

HCID 11430Potassium Carbonate

HCID 108221371-(Bromoacetyl)piperidine

HCID 67121454(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)-6a-methoxy-3-methyl-7,9,12,14-tetraoxo-5,6,6a,7,9,12,14,14a-octahydrobenzo[a]tetracene-2-carboxylate

Product 1

HCID 56601788(6R,6aS,14aR)-methyl 6,8,14a-trihydroxy-11-((2S,3R,4R,5R,6S)-4-hydroxy-3,5-dimethoxy-6-methyltetrahydro-2H-pyran-2-ylamino)-6a-methoxy-3-methyl-7,9,12,14-tetraoxo-1-(2-oxo-2-(piperidin-1-yl)ethoxy)-5,6,6a,7,9,12,14,14a-octahydrobenzo[a]tetracene-2-carboxylateYield 75.4%

Procedure

Following General Procedure: Method B using (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)-6a-methoxy-3-methyl-7,9,12,14-tetraoxo-5,6,6a,7,9,12,14,14a-octahydrobenzo[a]tetracene-2-carboxylate (35 mg, 0.050 mmol), potassium carbonate (21 mg, 0.15 mmol) and 2-bromo-1-(piperidin-1-yl)ethanone (31 mg, 0.15 mmol), the product was purified by preparative TLC (silica gel, 95:5 dichloromethane/methanol) to afford (6R,6aS,14aR)-methyl 6,8,14a-trihydroxy-11-((2S,3R,4R,5R,6S)-4-hydroxy-3,5-dimethoxy-6-methyltetrahydro-2H-pyran-2-ylamino)-6a-methoxy-3-methyl-7,9,12,14-tetraoxo-1-(2-oxo-2-(piperidin-1-yl)ethoxy)-5,6,6a,7,9,12,14,14a-octahydrobenzo[a]tetracene-2-carboxylate (31 mg, 75%) as a brown solid: 1H NMR (500 MHz, CDCl3) δ 14.17 (s, 1H), 8.28 (s, 1H), 6.85 (d, J=9.0 Hz, 1H), 6.81 (s, 1H), 5.87 (s, 1H), 5.82 (d, J=7.3 Hz, 1H), 4.95 (s, 1H), 4.68 (d, J=8.6 Hz, 1H), 4.59-4.50 (m, 2H), 4.00-3.74 (m, 2H), 3.78 (s, 3H), 3.74 (s, 3H), 3.69 (s, 1H), 3.60 (s, 6H), 3.40 (s, 3H), 3.35-3.25 (m, 4H), 3.12 (t, J=9.2 Hz, 1H), 2.54 (br s, 1H), 2.16 (s, 3H), 1.68 (br s, 2H), 1.62 (br s, 4H), 1.36 (d, J=6.1 Hz, 3H); MS (ESI+) m/z 823 (M+H); HPLC 98.7% (AUC), tR 16.81 min.

Workup

customthe product was purified by preparative TLC (silica gel, 95:5 dichloromethane/methanol)

Sources & evidence

ORD record: ord-774e98877a0c43ab974abc13fd67aa84
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08754054B2

Reaction notes

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