Methanol → HCID 90308660, compound

HRID 627750Notes

Reaction equation

HRID 627750 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH3:48])[C:6]([C:9]([NH:11][C:12]2[CH:13]=[CH:14][C:15]3[O:45][CH2:44][CH2:43][C@@H:19]4[S:20](=[O:42])(=[O:41])[C:21]([CH3:40])([CH3:39])[C:22]([N:24](C(OC(C)(C)C)=O)C(=O)OC(C)(C)C)=[N:23][C@:18]4([CH2:46][F:47])[C:16]=3[CH:17]=2)=[O:10])=[N:7][CH:8]=1)#[N:2].C(O)(C(F)(F)F)=O.CO>C(Cl)Cl>[NH2:24][C:22]1[C:21]([CH3:40])([CH3:39])[S:20](=[O:41])(=[O:42])[C@H:19]2[CH2:43][CH2:44][O:45][C:15]3[CH:14]=[CH:13][C:12]([NH:11][C:9](=[O:10])[C:6]4[C:5]([CH3:48])=[CH:4][C:3]([C:1]#[N:2])=[CH:8][N:7]=4)=[CH:17][C:16]=3[C@@:18]2([CH2:46][F:47])[N:23]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 6422Trifluoroacetic acidHCID 86728166HCID 86728166, compound

Product 1

HCID 90308660HCID 90308660, compoundYield 68.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a 50-mL round-bottomed flask was added tert-butyl N-[(4aS,11bS)-10-[(5-cyano-3-methyl-pyridine-2-carbonyl)amino]-11b-(fluoromethyl)-3,3-dimethyl-4,4-dioxo-5,6-dihydro-4aH-[1]benzoxepino[4,5-b][1,4]thiazin-2-yl]-N-tert-butoxycarbonyl-carbamate (129 mg, 0.188 mmol), DCM (3 mL), and TFA (2 mL). The reaction mixture stirred at RT for 30 min. The solvent was removed under vacuum. The reaction mixture was diluted with saturated aqueous NaHCO3 and extracted with DCM (3 mL) (3 times). The organic extract was dried over Na2SO4. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (12 g), eluting with a gradient of 0% to 2% 2M NH3.MeOH in DCM, to provide N-((4aS,11bS)-2-amino-11b-(fluoromethyl)-3,3-dimethyl-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-10-yl)-5-cyano-3-methylpicolinamide (62 mg, 0.128 mmol, 67.9% yield) as an off-white solid. MS m/z=486.0 (M+H).

Workup

  1. customThe solvent was removed under vacuum
  2. additionThe reaction mixture was diluted with saturated aqueous NaHCO3
  3. extractionextracted with DCM (3 mL) (3 times)
  4. extractionThe organic extract
  5. dry with materialwas dried over Na2SO4
  6. customThe crude material was absorbed onto a plug of silica gel
  7. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (12 g)
  8. washeluting with a gradient of 0% to 2% 2M NH3

Sources & evidence

ORD record
ord-0436e664af7947beaeb38de80338cb82
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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