Water → HCID 90308661, compound

HRID 627756Notes

Reaction equation

HRID 627756 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH3:46])[C:5]([C:8]([NH:10][C:11]2[CH:12]=[CH:13][C:14]3S[CH2:43][CH2:42][C@H:18]4[S:19](=O)(=[O:40])[C:20]([CH3:39])([CH3:38])[C:21]([N:23](C(OC(C)(C)C)=O)C(=O)OC(C)(C)C)=[N:22][C@:17]4([CH3:45])[C:15]=3[CH:16]=2)=[O:9])=[N:6][CH:7]=1.C1COCC1.O[O:53][S:54]([O-:56])=O.[K+].C(O)(C(F)(F)F)=O.[OH2:65]>CCOC(C)=O.CO>[NH2:23][C:21]1[C:20]([CH3:38])([CH3:39])[S:19](=[O:40])(=[O:65])[C@@H:18]2[CH2:42][CH2:43][S:54](=[O:56])(=[O:53])[C:14]3[CH:13]=[CH:12][C:11]([NH:10][C:8](=[O:9])[C:5]4[C:4]([CH3:46])=[CH:3][C:2]([Cl:1])=[CH:7][N:6]=4)=[CH:16][C:15]=3[C@@:17]2([CH3:45])[N:22]=1

Participants

8

Reactant 5

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 8028TetrahydrofuranHCID 23707502Potassium hydroxy sulfiteHCID 90301428HCID 90301428, compound

Product 1

HCID 90308661HCID 90308661, compoundYield 51.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A vial was charged with tert-butyl N-[(4aR,11bR)-10-[(5-chloro-3-methyl-pyridine-2-carbonyl)amino]-3,3,11b-trimethyl-4,4-dioxo-5,6-dihydro-4aH-[1]benzothiepino[4,5-b][1,4]thiazin-2-yl]-N-tert-butoxycarbonyl-carbamate (90 mg, 0.130 mmol), THF (556 μl) water (185 μl) and MeOH (556 μl). Oxone (239 mg, 0.389 mmol) was added, and the mixture was stirred at RT for 72 h. Water and EtOAc were added, and the layers were separated. The organic portion was dried, filtered and concentrated. The crude material was dissolved in 1 mL DCM, and TFA (200 μl, 2.60 mmol) was added. The reaction was stirred at RT for 2 h. The solution was loaded onto an SCX column and washed with MeOH. The free base was eluted with ammonia/MeOH. The filtrate was concentrated, and the crude material was triturated in EtOAc, filtered, washed with EtOAc and dried to provide N-((4aR,11bR)-2-amino-3,3,11b-trimethyl-4,4,7,7-tetraoxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]thiepino[4,5-b][1,4]thiazin-10-yl)-5-chloro-3-methylpicolinamide (35 mg, 0.067 mmol, 51.3% yield) as a white solid. LC/MS (ESI+) m/z=525.1 (M+Na).

Workup

  1. customthe layers were separated
  2. customThe organic portion was dried
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe crude material was dissolved in 1 mL DCM
  6. stirringThe reaction was stirred at RT for 2 h
  7. washwashed with MeOH
  8. washThe free base was eluted with ammonia/MeOH
  9. concentrationThe filtrate was concentrated
  10. customthe crude material was triturated in EtOAc
  11. filtrationfiltered
  12. washwashed with EtOAc
  13. customdried

Sources & evidence

ORD record
ord-2298b414cd34491c80fadeef4df75841
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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