4-Methylmorpholine → HCID 53240856, compound

HRID 422184Notes

Reaction equation

HRID 422184 reaction equation
[OH:1][C:2]1[CH:19]=[C:18]2[C:5]([C@@:6]3([CH3:25])[C@H:15]([CH2:16][S:17]2(=[O:21])=[O:20])[C@:14]2([CH3:22])[C@H:9]([C:10]([CH3:24])([CH3:23])[CH2:11][CH2:12][CH2:13]2)[CH2:8][CH2:7]3)=[C:4]([C:26]([OH:28])=O)[CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[CH3:60][N:61]1[CH2:66][CH2:65][NH:64][CH2:63][CH2:62]1>C1COCC1.CN(C=O)C>[OH:1][C:2]1[CH:19]=[C:18]2[C:5]([C@@:6]3([CH3:25])[C@H:15]([CH2:16][S:17]2(=[O:21])=[O:20])[C@:14]2([CH3:22])[C@H:9]([C:10]([CH3:24])([CH3:23])[CH2:11][CH2:12][CH2:13]2)[CH2:8][CH2:7]3)=[C:4]([C:26]([N:64]2[CH2:65][CH2:66][N:61]([CH3:60])[CH2:62][CH2:63]2)=[O:28])[CH:3]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 531671-MethylpiperazineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 53240650HCID 53240650, compound

Product 1

HCID 53240856HCID 53240856, compoundYield 35.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of (1R,10R,11S,16S)-5-hydroxy-1,11,15,15-tetramethyl-8,8-dioxo-8λ6-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-3-carboxylic acid (65) (0.20 g, 0.49 mmol), HATU (0.37 g, 0.98 mmol), N-methylmorpholine (0.10 mL, 1.5 mmol) and 1-methyl piperazine (0.15 mL, 1.5 mmol) in THF (10 mL) and DMF (2.0 mL) was stirred at room temperature for 18 h. The THF was evaporated under reduced pressure, the residue was quenched with water and the resulted solid was collected by filtration. The crude product was purified by flash column chromatography on silica gel (CH2Cl2/MeOH, 10:1). The resulting material was further purified by preparative HPLC (NH4OAc/CH3CN) to give (1R,10R,11S,16S)-5-hydroxy-1,11,15,15-tetramethyl-3-[(4-methylpiperazin-1-yl)carbonyl]-8λ6-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-8,8-dione (94) (0.085 g, 34%) as a white solid. 1H NMR (CDCl3): δ 7.29 (d, 1H), 6.77 (d, 1H), 3.62-3.20 (m, 5H), 2.70-2.00 (m, 10H), 1.78-1.24 (m, 10H), 1.20-1.00 (m, 2H), 0.99-0.92 (m, 4H), 0.88 (s, 3H), 0.82 (s, 3H). MS m/z 489 (C27H40N2O4S+H+).

Workup

  1. customThe THF was evaporated under reduced pressure
  2. customthe residue was quenched with water
  3. filtrationthe resulted solid was collected by filtration
  4. customThe crude product was purified by flash column chromatography on silica gel (CH2Cl2/MeOH, 10:1)
  5. customThe resulting material was further purified by preparative HPLC (NH4OAc/CH3CN)

Sources & evidence

ORD record
ord-caf2e8f761b748af9add22d62dde4134
Source dataset
uspto-grants-2012_01
Patent number
US08101605B2

Reaction notes

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