Methylamine → (1R,10S,11S,16S)-3-methoxy-N,11,15,15-tetramethyl-8,8-dioxo-8lambda6thiatetracyclo[8.8.0.02,7.011,16]-octadeca-2,4,6-triene-5-carboxamide

HRID 422160Notes

Reaction equation

HRID 422160 reaction equation
[CH3:1][O:2][C:3]1[CH:20]=[C:19]([C:21](O)=[O:22])[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:30](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.CN>CN(C=O)C.C1COCC1>[CH3:1][O:2][C:3]1[CH:20]=[C:19]([C:21]([NH:30][CH3:29])=[O:22])[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

Participants

7

Reactant 4

HCID 6329MethylamineHCID 79724-MethylmorpholineHCID 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 86654191(1R,10S,11S,16S)-3-methoxy-N,11,15,15-tetramethyl-8,8-dioxo-8lambda6thiatetracyclo[8.8.0.02,7.011,16]-octadeca-2,4,6-triene-5-carboxamideYield 74.7%

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) (0.35 g, 0.83 mmol), HATU (0.61 g, 1.7 mmol), N-methylmorpholine (0.18 mL, 2.5 mmol), methylamine (2 M in THF, 1.04 mL, 2.08 mmol), THF (10.0 mL) and DMF (2.0 mL) in a sealed tube was stirred at room temperature for 18 h. The THF was evaporated and the residue was quenched with water. The resulting solid was collected by filtration. The crude product was purified by flash chromatography on silica gel (Hexanes/EtOAc, 1:1) to yield (1R,10S,11S,16S)-3-methoxy-N,11,15,15-tetramethyl-8,8-dioxo-8λ6thiatetracyclo[8.8.0.02,7.011,16]-octadeca-2,4,6-triene-5-carboxamide (0.26 g, 74%) (Compound No. 62) as a white solid. 1H NMR (CDCl3): δ 8.77 (s, 1H), 8.07 (s, 1H), 7.60 (s, 1H), 6.59 (m, 1H), 3.52 (m, 1H), 3.37 (m, 1H), 3.24 (m, 1H), 3.05 (d, 3H), 2.32 (d, 1H), 1.65-1.10 (m, 13H), 0.97 (s, 3H), 0.88 (s, 3H), 0.84 (s, 3H). MS m/z 420 (C23H33NO4S+H+).

Workup

  1. customThe THF was evaporated
  2. customthe residue was quenched with water
  3. filtrationThe resulting solid was collected by filtration
  4. customThe crude product was purified by flash chromatography on silica gel (Hexanes/EtOAc, 1:1)

Sources & evidence

ORD record
ord-7024bbf5c7fe4125ac66f9cf9610d6f0
Source dataset
uspto-grants-2012_01
Patent number
US08101605B2

Reaction notes

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