Cyclohexylamine → HCID 67121382, compound

HRID 406145Notes

Reaction equation

HRID 406145 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]2[CH:57]=[CH:58][CH:59]=[CH:60][C:55]=2N=N1.C1(N)CCCCC1>C1COCC1>[CH:56]1([NH:52][C:47]([C:3]2[C:4]([CH3:46])=[CH:5][C:6]3[CH2:23][C@@H:22]([OH:24])[C@:21]4([O:25][CH3:26])[C@@:8]([OH:45])([C:9](=[O:44])[C:10]5[C:19]([C:20]4=[O:27])=[C:18]([OH:28])[C:17]4[C:16](=[O:29])[CH:15]=[C:14]([NH:30][CH:31]6[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]6)[C:13](=[O:43])[C:12]=4[CH:11]=5)[C:7]=3[C:2]=2[OH:1])=[O:49])[CH2:57][CH2:58][CH2:59][CH2:60][CH2:55]1

Participants

5

Reactant 3

HCID 7965CyclohexylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 67121425HCID 67121425, compound

Product 1

HCID 67121382HCID 67121382, compound

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 (60 mg, 0.09 mmol) in THF (2 mL) was added polystyrene-carbodiimide (156 mg, 0.18 mmol), 1-hydroxybenzotriazole hydrate (24 mg, 0.18 mmol) and cyclohexylamine (10 mg, 0.13 mmol). 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)—N-cyclohexyl-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-carboxamide as a mixture of diastereomers (14 mg, 20%) and as a dark red solid: 1H NMR (500 MHz, CD3OD) δ 8.10 (s, 1H), 6.59 (s, 1H), 6.15 (s, 0.3H), 6.00 (s, 0.7H), 5.19 (s, 0.3H), 4.95 (s, 0.7H), 4.89 (br s, 1H), 3.95-3.90 (m, 1H), 3.75 (s, 3H), 3.74-3.71 (m, 0.7H), 3.70-3.68 (m, 0.3H), 3.67-3.64 (m, 1H), 3.58 (s, 3H), 3.53 (s, 1H), 3.50 (s, 2H), 3.48-3.35 (m, 5H), 3.27-3.20 (m, 1H), 3.09-3.02 (m, 1H), 2.22 (s, 3H), 1.93-1.81 (m, 2H), 1.80-1.69 (m, 2H), 1.66-1.57 (m, 1H), 1.40-1.33 (m, 2H), 1.27 (d, J=6.5 Hz, 2H), 1.22 (d, J=6.5 Hz, 1H), 1.19-1.15 (m, 2H); MS (ESI+) m/z 765 (M+H); HPLC 95.4% (AUC), tR 13.79 min.

Workup

  1. filtrationThe reaction was filtered through
  2. filtrationa micro filter
  3. concentrationconcentrated
  4. 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-b42355a6acc44deca88f6c339dab9f1a
Source dataset
uspto-grants-2014_06
Patent number
US08754054B2

Reaction notes

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