Ammonia → HCID 86660838, compound

HRID 406147Notes

Reaction equation

HRID 406147 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.O[N:52]1C2C=CC=CC=2N=N1.N>C1COCC1.[Pd]>[OH:1][C:2]1[C:7]2[C:8]3([OH:45])[C:21]([O:25][CH3:26])([CH:22]([OH:24])[CH2:23][C:6]=2[CH:5]=[C:4]([CH3:46])[C:3]=1[C:47]([NH2:52])=[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[CH: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

6

Reactant 3

HCID 222AmmoniaHCID 27960291-Hydroxybenzotriazole hydrateHCID 67121425HCID 67121425, compound

Product 1

HCID 86660838HCID 86660838, compoundYield 15%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent2×

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 (100 mg, 0.15 mmol) in THF (2 mL) was added 10% Pd/C and the reaction mixture was stirred at room temperature under hydrogen at 1 atmosphere for 4 h. The reaction mixture was filtered without exposure to air into another flask containing polystyrene-carbodiimide (260 mg, 0.29 mmol) and the mixture was stirred for 10 min. A solution of 1-hydroxybenzotriazole hydrate (40 mg, 22 mmol) in THF (1 mL) and ammonia (0.22 mL, 2.0 M solution in THF, 0.16 mmol) were added and the reaction mixture was stirred at room temperature under nitrogen for 4 h. The reaction was filtered through a micro filter and concentrated. 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) to afford 6R,6aS,14aR)-1,6,8,14a-tetrahydroxy-11-((2S,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-carboxamide (12 mg, 15%) as a dark red solid: 1H NMR (500 MHz, CDCl3) δ 14.19 (s, 1H), 12.89 (s, 1H), 8.22 (s, 1H), 6.86 (d, J=8.5 Hz, 1H), 6.52 (s, 1H), 5.96 (s, 2H), 5.87 (s, 1H), 4.96 (d, J=6.0 Hz, 1H), 4.68 (d, J=9.0 Hz, 1H), 3.79 (s, 3H), 3.78-3.66 (m, 3H), 3.61 (s, 3H), 3.59-3.50 (m, 2H), 3.40 (s, 3H), 3.37-3.30 (m, 3H), 3.13 (t, J=9.5 Hz, 1H), 2.46 (s, 3H), 1.36 (s, 3H); MS (ESI+) m/z 683 (M+H); HPLC 94.3% (AUC), tR 11.64 min.

Workup

  1. filtrationThe reaction mixture was filtered without exposure to air into another flask
  2. stirringthe mixture was stirred for 10 min
  3. stirringthe reaction mixture was stirred at room temperature under nitrogen for 4 h
  4. filtrationThe reaction was filtered through
  5. filtrationa micro filter
  6. concentrationconcentrated
  7. 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-e8f5acf682b5448f85f56d3d787a63c0
Source dataset
uspto-grants-2014_06
Patent number
US08754054B2

Reaction notes

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