4-Methylmorpholine → (1R,10R,11S,16S)-3-hydroxy-1,11,15,15-tetramethyl-5-[(4-methyl piperazin-1-yl)-carbonyl]-8lambda6-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-8,8-dione

HRID 422179Notes

Reaction equation

HRID 422179 reaction equation
C[O:2][C:3]1[CH:20]=[C:19]([C:21]([OH:23])=O)[CH:18]=[C:17]2[C:4]=1[C@H:5]1[C@H:14]([CH2:15][S:16]2(=[O:25])=[O:24])[C@:13]2([CH3:26])[C@H:8]([C:9]([CH3:28])([CH3:27])[CH2:10][CH2:11][CH2:12]2)[CH2:7][CH2:6]1.[CH3:29]N(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:2][C:3]1[CH:20]=[C:19]([C:21]([N:64]2[CH2:65][CH2:66][N:61]([CH3:60])[CH2:62][CH2:63]2)=[O:23])[CH:18]=[C:17]2[C:4]=1[C@@:5]1([CH3:29])[C@H:14]([CH2:15][S:16]2(=[O:24])=[O:25])[C@:13]2([CH3:26])[C@H:8]([C:9]([CH3:28])([CH3:27])[CH2:10][CH2:11][CH2:12]2)[CH2:7][CH2:6]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 86654189(1R,10S,11S,16S)-3-methoxy-11,15,15-trimethyl-8,8-dioxo-8lambda6-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-5-carboxylic acid

Product 1

HCID 53240855(1R,10R,11S,16S)-3-hydroxy-1,11,15,15-tetramethyl-5-[(4-methyl piperazin-1-yl)-carbonyl]-8lambda6-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-8,8-dioneYield 54.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of (1R,10S,11S,16S)-3-methoxy-11,15,15-trimethyl-8,8-dioxo-8λ6-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-5-carboxylic acid (61) (0.20 g, 0.49 mmol), HATU (0.37 g, 0.98 mmol), N-methylmorpholine (0.10 mL, 1.5 mmol) and 1-methylpiperazine (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 resulting solid was collected by filtration. The crude product was purified by flash column chromatography on silica gel (CH2Cl2/MeOH, 10:1) to give (1R,10R,11S,16S)-3-hydroxy-1,11,15,15-tetramethyl-5-[(4-methyl piperazin-1-yl)-carbonyl]-8λ6-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-8,8-dione (89) (0.13 g, 54%) as a white solid. 1H NMR (CDCl3): δ 9.55 (s, 1H), 7.23 (d, 1H), 7.07 (d, 1H), 3.84 (m, 2H), 3.49 (m, 2H), 3.18 (m, 3H), 2.52 (m, 2H), 2.38 (m, 2H), 2.33 (s, 3H), 2.15 (d, 1H), 1.78-1.32 (m, 6H), 1.28 (s, 3H), 1.24-1.05 (m, 2H), 0.98 (m, 1H), 0.90 (s, 6H), 0.86 (m, 1H), 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 resulting solid was collected by filtration
  4. customThe crude product was purified by flash column chromatography on silica gel (CH2Cl2/MeOH, 10:1)

Sources & evidence

ORD record
ord-0c1f1719b2a24bc5bc5ea312aa191343
Source dataset
uspto-grants-2012_01
Patent number
US08101605B2

Reaction notes

Loading…