Trifluoroacetic acid → HCID 90308642, compound

HRID 627745Notes

Reaction equation

HRID 627745 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]([C:8]([NH:10][C:11]2[CH:12]=[CH:13][C:14]3[O:44][CH2:43][CH2:42][C@H:18]4[S:19](=[O:41])(=[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.CC(C)([O-])C.[K+].[CH2:52]([OH:55])[C:53]#[CH:54].C(O)(C(F)(F)F)=O>CN(C=O)C.C(Cl)Cl>[NH2:23][C:21]1[C:20]([CH3:38])([CH3:39])[S:19](=[O:41])(=[O:40])[C@@H:18]2[CH2:42][CH2:43][O:44][C:14]3[CH:13]=[CH:12][C:11]([NH:10][C:8]([C:5]4[CH:4]=[N:3][C:2]([O:55][CH2:52][C:53]#[CH:54])=[CH:7][N:6]=4)=[O:9])=[CH:16][C:15]=3[C@@:17]2([CH3:45])[N:22]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7859Propargyl alcoholHCID 23665647Potassium tert-butoxideHCID 90308597HCID 90308597, compound

Product 1

HCID 90308642HCID 90308642, compoundYield 89.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of tert-butyl N-[(4aR,11bR)-10-[(5-chloropyrazine-2-carbonyl)amino]-3,3,11b-trimethyl-4,4-dioxo-5,6-dihydro-4aH-[1]benzoxepino[4,5-b][1,4]thiazin-2-yl]-N-tert-butoxycarbonyl-carbamate (126 mg, 0.190 mmol) in DMF (2 mL) was added a mixture of potassium tert-butoxide (63.9 mg, 0.569 mmol) in propargyl alcohol (0.224 mL, 3.79 mmol). The reaction was stirred at ambient temperature for 1 h. The reaction mixture was partitioned between water and ethyl acetate, and the organic layer was concentrated. The crude residue was diluted with DCM (3 mL) and TFA (0.292 mL, 3.79 mmol) was added and the reaction was stirred at ambient temperature. After 1 h, the reaction mixture was diluted with DCM, washed with saturated aqueous sodium bicarbonate, and concentrated. The crude product was purified by column chromatography, eluting with 20-80% (3:1 ethyl acetate/ethanol) in heptane, to provide N-((4aR,11bR)-2-amino-3,3,11b-trimethyl-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-10-yl)-5-(prop-2-yn-1-yloxy)pyrazine-2-carboxamide (82 mg, 0.170 mmol, 89% yield) as an off-white powder. MS m/z=484.0 (M+H).

Workup

  1. customThe reaction mixture was partitioned between water and ethyl acetate
  2. concentrationthe organic layer was concentrated
  3. additionwas added
  4. stirringthe reaction was stirred at ambient temperature
  5. waitAfter 1 h
  6. washwashed with saturated aqueous sodium bicarbonate
  7. concentrationconcentrated
  8. customThe crude product was purified by column chromatography
  9. washeluting with 20-80% (3:1 ethyl acetate/ethanol) in heptane

Sources & evidence

ORD record
ord-af16fa5a792844979b6e6d335c8f2453
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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