3-Amino-1-propanol → HCID 178497452, compound

HRID 406161Notes

Reaction equation

HRID 406161 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(=O)C=2C=1O)[C:9]3=[O:44].[NH2:51][CH2:52][CH2:53][CH2:54][OH:55]>CO>[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:52](=[N:51]\[CH2:4][CH2:3][CH2:2][OH:1])/[C:53]=2[C:54]=1[OH:55])[C:9]3=[O:44]

Participants

4

Reactant 2

HCID 90863-Amino-1-propanolHCID 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 178497452HCID 178497452, compoundYield 116%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a 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)-6a-methoxy-3-methyl-7,9,12,14-tetraoxo-5,6,6a,7,9,12,14,14a-octahydrobenzo[a]tetracene-2-carboxylate (100 mg, 0.14 mmol) in methanol (3 mL) was added 3-aminopropan-1-ol (107 mg, 1.43 mmol). The reaction mixture was stirred at room temperature under nitrogen for 2 h. The reaction was quenched by adding saturated ammonium chloride solution (25 mL). Then it was extracted with chloroform (75 mL) and washed with water (2×25 mL). The organic layer was separated, dried (MgSO4), filtered and concentrated to give the crude product. The crude material was purified by preparative TLC (silica gel, 90:10 chloroform/methanol) to afford (6R,6aS,14aR,E)-methyl 1,6,8,14a-tetrahydroxy-11-((2S,3R,4R,5R,6S)-4-hydroxy-3,5-dimethoxy-6-methyltetrahydro-2H-pyran-2-ylamino)-9-(3-hydroxypropylimino)-6a-methoxy-3-methyl-7,12,14-trioxo-5,6,6a,7,9,12,14,14a-octahydrobenzo[a]tetracene-2-carboxylate (61.3 mg, 56.6%) as a dark blue solid: 1H NMR (500 MHz, CDCl3) δ 11.94 (s, 1H), 7.89 (s, 1H), 6.94 (d, J=8.5 Hz, 1H), 6.48 (s, 1H), 6.12 (s, 1H), 5.27 (s, 1H), 5.02-4.99 (m, 1H), 4.74 (d, J=9.5 Hz, 2H), 4.12 (dd, J=14.2, 7.1 Hz, 2H), 3.83 (s, 3H), 3.81-3.72 (m, 9H), 3.68 (br s, 1H), 3.60 (s, 3H), 3.40 (s, 4H), 3.13 (t, J=9.1 Hz, 1H), 2.53 (s, 1H), 2.36 (s, 3H), 2.02-2.00 (m, 2H), 1.36 (d, J=6.0 Hz, 3H); MS (ESI+) m/z 755 (M+H); HPLC 97.5% (AUC), tR=10.36 min.

Workup

  1. customThe reaction was quenched
  2. additionby adding saturated ammonium chloride solution (25 mL)
  3. extractionThen it was extracted with chloroform (75 mL)
  4. washwashed with water (2×25 mL)
  5. customThe organic layer was separated
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give the crude product
  10. customThe crude material was purified by preparative TLC (silica gel, 90:10 chloroform/methanol)

Sources & evidence

ORD record
ord-6845b5fc79fb4781834e0edbadf816ac
Source dataset
uspto-grants-2014_06
Patent number
US08754054B2

Reaction notes

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