HCID 89573786, compound → HCID 89260757, compound

HRID 1911008Notes

Reaction equation

HRID 1911008 reaction equation
[N:1]([C:4]1[CH:25]=[C:24]2[C:7]([CH2:8][CH2:9][C@@H:10]3[CH2:15][S:14][C:13]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[N:12][C@@:11]32[CH3:26])=[CH:6][CH:5]=1)=[N+]=[N-]>[Pd].CO>[C:19]([O:18][C:17](=[O:23])[NH:16][C:13]1[S:14][CH2:15][C@H:10]2[CH2:9][CH2:8][C:7]3[C:24](=[CH:25][C:4]([NH2:1])=[CH:5][CH:6]=3)[C@@:11]2([CH3:26])[N:12]=1)([CH3:22])([CH3:20])[CH3:21]

Participants

4

Reactant 1

HCID 89573786HCID 89573786, compound

Product 1

HCID 89260757HCID 89260757, compoundYield 101.8%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

10% Palladium on carbon (54 mg, 0.051 mmol) was added to a flask charged with a solution of tert-butyl rel-((4aS,10bS)-9-azido-10b-methyl-4a,5,6,10b-tetrahydro-4H-naphtho[1,2-d][1,3]thiazin-2-yl)carbamate from step D1 (190 mg, 0.509 mmol) in methanol (40 mL) under dry nitrogen. The vessel was repeatedly flushed with hydrogen gas. The reaction mixture was allowed to stir under a balloon of hydrogen gas for 20 h. The vessel was flushed with nitrogen. The contents were filtered through celite. The celite and vessel were rinsed with methanol. The combined filtrates were concentrated in vacuo. The residue was dried under high vacuum to afford tert-butyl((4aS,10bS)-9-amino-10b-methyl-4a,5,6,10b-tetrahydro-4H-naphtho[1,2-d][1,3]thiazin-2-yl)carbamate (180 mg, 0.518 mmol, 100% yield) as a gray oil. LCMS (M+Na)+=270.1. 1H NMR (500 MHz, chloroform-d) δ 6.89 (d, J=8.1 Hz, 1H), 6.81-6.72 (m, 1H), 6.58 (dd, J=8.1, 2.4 Hz, 1H), 3.66 (br. s, 2H), 3.03 (dd, J=13.0, 3.7 Hz, 1H), 2.92 (dd, J=12.9, 8.3 Hz, 1H), 2.77 (t, J=6.9 Hz, 2H), 2.26 (dt, J=7.2, 3.6 Hz, 1H), 2.11 (dtd, J=14.0, 7.1, 3.6 Hz, 1H), 1.97 (dq, J=13.7, 6.7 Hz, 1H), 1.63 (s, 3H), 1.49 (s, 9H).

Workup

  1. customThe vessel was repeatedly flushed with hydrogen gas
  2. customThe vessel was flushed with nitrogen
  3. filtrationThe contents were filtered through celite
  4. washThe celite and vessel were rinsed with methanol
  5. concentrationThe combined filtrates were concentrated in vacuo
  6. customThe residue was dried under high vacuum

Sources & evidence

ORD record
ord-24e063ce1953431f9401c4a83ff128a3
Source dataset
uspto-grants-2013_12
Patent number
US08604024B2

Reaction notes

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