Methylamine → (1R,10R,11S,16S)-5-methoxy-N,1,11,15,15-pentamethyl-8-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-3-carboxamide

HRID 422169Notes

Reaction equation

HRID 422169 reaction equation
[CH3:1][O:2][C:3]1[CH:20]=[C:19]2[C:6]([C@@:7]3([CH3:24])[C@H:16]([CH2:17][S:18]2)[C@:15]2([CH3:21])[C@H:10]([C:11]([CH3:23])([CH3:22])[CH2:12][CH2:13][CH2:14]2)[CH2:9][CH2:8]3)=[C:5]([C:25]([OH:27])=O)[CH:4]=1.[CH3:28][N:29](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.CN>C1COCC1.CN(C=O)C>[CH3:1][O:2][C:3]1[CH:20]=[C:19]2[C:6]([C@@:7]3([CH3:24])[C@H:16]([CH2:17][S:18]2)[C@:15]2([CH3:21])[C@H:10]([C:11]([CH3:23])([CH3:22])[CH2:12][CH2:13][CH2:14]2)[CH2:9][CH2:8]3)=[C:5]([C:25]([NH:29][CH3:28])=[O:27])[CH:4]=1

Participants

7

Reactant 4

HCID 6329MethylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58294803(1R,10R,11S,16S)-5-methoxy-1,11,15,15-tetramethyl-8-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-3-carboxylic acid

Product 1

HCID 58294801(1R,10R,11S,16S)-5-methoxy-N,1,11,15,15-pentamethyl-8-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-3-carboxamideYield 60.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of (1R,10R,11S,16S)-5-methoxy-1,11,15,15-tetramethyl-8-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-3-carboxylic acid (74) (0.13 g, 0.33 mmol) in anhydrous THF (10 mL) and anhydrous DMF (0.7 mL), was prepared under N2. To the solution, HATU (0.15 g, 0.40 mmol) and Hunig's base (0.08 mL, 0.4 mmol) were added. The mixture was stirred at room temperature for 1 h. MeNH2 (2 M in THF, 2.0 mL, 4.0 mmol) was added and the flask was sealed and stirred at room temperature for 24 h. The reaction mixture was concentrated, and the residue was dissolved in CH2Cl2 and washed with saturated aqueous sodium bicarbonate. The aqueous phase was extracted with CH2Cl2. The combined organic extracts were washed with brine and concentrated to dryness. The crude product was purified by flash chromatography on silica gel (CH2Cl2/EtOAc, 5:1) to yield (1R,10R,11S,16S)-5-methoxy-N,1,11,15,15-pentamethyl-8-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-3-carboxamide (75) (0.08 g, 59%) as a white solid.

Workup

  1. customthe flask was sealed
  2. stirringstirred at room temperature for 24 h
  3. concentrationThe reaction mixture was concentrated
  4. dissolutionthe residue was dissolved in CH2Cl2
  5. washwashed with saturated aqueous sodium bicarbonate
  6. extractionThe aqueous phase was extracted with CH2Cl2
  7. washThe combined organic extracts were washed with brine
  8. concentrationconcentrated to dryness
  9. customThe crude product was purified by flash chromatography on silica gel (CH2Cl2/EtOAc, 5:1)

Sources & evidence

ORD record
ord-55203f81c161410d9e8c29edd0ce8aa7
Source dataset
uspto-grants-2012_01
Patent number
US08101605B2

Reaction notes

Loading…