Methylamine → HCID 67121351, compound

HRID 406146Notes

Reaction equation

HRID 406146 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]([OH:49])=O)[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]1[C:56]2C=CC=CC=2N=N1.CN>C1COCC1.[Pd]>[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]([NH:52][CH3:56])=[O:49])[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

6

Reactant 3

HCID 6329MethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 67121425HCID 67121425, compound

Product 1

HCID 67121351HCID 67121351, compound

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 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 methylamine (0.08 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-((3R,4R,5R,6S)-4-hydroxy-3,5-dimethoxy-6-methyltetrahydro-2H-pyran-2-ylamino)-6a-methoxy-N,3-dimethyl-7,9,12,14-tetraoxo-5,6,6a,7,9,12,14,14a-octahydrobenzo[a]tetracene-2-carboxamide as a mixture of diastereomers (7.5 mg, 7%) and as a dark red solid: 1H NMR (500 MHz, CD3OD) δ 8.11 (s, 1H), 6.59 (s, 1H), 6.15 (s, 0.3H), 5.99 (s, 0.7H), 5.19-5.17 (m, 0.3H), 4.94 (s, 0.7H), 3.75 (s, 3H), 3.57 (s, 3H), 3.54 (s, 1H), 3.51 (s, 1H), 3.48-3.35 (m, 6H), 3.26-3.21 (m, 1H), 3.08 (t, J=9.0 Hz, 0.3H), 3.04 (t, J=9.0 Hz, 0.7H), 2.78 (s, 3H), 2.22 (s, 3H), 1.27 (d, J=9.0 Hz, 2H), 1.22 (d, J=6.5 Hz, 1H); MS (ESI+) m/z 697 (M+H); HPLC >99% (AUC), tR 10.63 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-dc1cf33247d84b5c89cd05debe679586
Source dataset
uspto-grants-2014_06
Patent number
US08754054B2

Reaction notes

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