2,3-Dichloropyridine → HCID 89573616, compound

HRID 1911041Notes

Reaction equation

HRID 1911041 reaction equation
CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C.Cl[C:40]1[C:45]([Cl:46])=[CH:44][CH:43]=[CH:42][N:41]=1.[NH2:47][C:48]1[CH:71]=[CH:70][C:51]2[O:52][CH2:53][CH2:54][C@@H:55]3[CH2:60][S:59][C:58]([NH:61][C:62](=[O:68])[O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[N:57][C@:56]3([CH3:69])[C:50]=2[CH:49]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+]>[Cl:46][C:45]1[C:40]([NH:47][C:48]2[CH:71]=[CH:70][C:51]3[O:52][CH2:53][CH2:54][C@@H:55]4[CH2:60][S:59][C:58]([NH:61][C:62](=[O:68])[O:63][C:64]([CH3:65])([CH3:66])[CH3:67])=[N:57][C@:56]4([CH3:69])[C:50]=3[CH:49]=2)=[N:41][CH:42]=[CH:43][CH:44]=1

Participants

6

Reactant 4

HCID 169882,3-DichloropyridineHCID 2733832Lithium HexamethyldisilazideHCID 25112535BrettphosHCID 89260758HCID 89260758, compound

Product 1

HCID 89573616HCID 89573616, compoundYield 99%

Reagents, catalysts & solvents 1

HCID 25112666BrettPhos PalladacycleCatalyst

Procedure

An oven dried vial was charged with brettphos precatalyst (12 mg, 0.014 mmol), brettphos (7.6 mg, 0.014 mmol), 2,3-dichloropyridine (8.5 mg, 0.058 mmol), tert-butyl rel-((4aS,11bS)-10-amino-11b-methyl-4a,5,6,11b-tetrahydro-4H-benzo[2,3]oxepino[4,5-d][1,3]thiazin-2-yl)carbamate from preparation I (25 mg, 0.069 mmol) and LiHMDS (14 mg, 0.086 mmol). The vial was purged with nitrogen. Dioxane (1 mL) was added. The vial was placed in a preheated oil bath at 100° C. for 1 h. The reaction was then diluted with ethyl acetate and saturated aqueous ammonium chloride solution. The organic layer was washed with water, brine, and dried over sodium sulfate. The organic layer was filtered and concentrated in vacuo to afford tert-butyl rel-((4aS,11bS)-10-((3-chloropyridin-2-yl)amino)-11b-methyl-4a,5,6,11b-tetrahydro-4H-benzo[2,3]oxepino[4,5-d][1,3]thiazin-2-yl)carbamate (27 mg, 0.057 mmol, 99% yield). The crude material was used in the next step without further purification. MS (M+H)+=475.26.

Workup

  1. customAn oven dried vial
  2. customThe vial was purged with nitrogen
  3. additionDioxane (1 mL) was added
  4. additionThe reaction was then diluted with ethyl acetate and saturated aqueous ammonium chloride solution
  5. washThe organic layer was washed with water, brine
  6. dry with materialdried over sodium sulfate
  7. filtrationThe organic layer was filtered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3490657bf48e4bd4b5699148075024c0
Source dataset
uspto-grants-2013_12
Patent number
US08604024B2

Reaction notes

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