1,8-Diazabicyclo(5.4.0)undec-7-ene → (1r)-3-[7-(Azidomethyl)-1,1-dioxido-4h-thieno[2,3-e][1,2,4]thiadiazin-3-yl]-1-(3,3-dimethylbutyl)-4-hydroxy-1-methylnaphthalen-2(1h)-one

HRID 494671Notes

Reaction equation

HRID 494671 reaction equation
[CH3:1][C:2]([CH3:32])([CH3:31])[CH2:3][CH2:4][C@:5]1([CH3:30])[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([OH:15])=[C:7]([C:16]2[NH:21][C:20]3[S:22][CH:23]=[C:24]([CH2:25]O)[C:19]=3[S:18](=[O:28])(=[O:27])[N:17]=2)[C:6]1=[O:29].N12CCCN=C1CCCCC2.C1(P([N:58]=[N+:59]=[N-:60])(C2C=CC=CC=2)=O)C=CC=CC=1>ClCCl>[N:58]([CH2:25][C:24]1[C:19]2[S:18](=[O:28])(=[O:27])[N:17]=[C:16]([C:7]3[C:6](=[O:29])[C@@:5]([CH2:4][CH2:3][C:2]([CH3:32])([CH3:31])[CH3:1])([CH3:30])[C:14]4[C:9]([C:8]=3[OH:15])=[CH:10][CH:11]=[CH:12][CH:13]=4)[NH:21][C:20]=2[S:22][CH:23]=1)=[N+:59]=[N-:60]

Participants

5

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 199401P,P-Diphenylphosphinic azideHCID 135953291(1r)-1-(3,3-Dimethylbutyl)-4-hydroxy-3-[7-(hydroxymethyl)-1,1-dioxido-4h-thieno[2,3-e][1,2,4]thiadiazin-3-yl]-1-methylnaphthalen-2(1h)-one

Product 1

HCID 137194540(1r)-3-[7-(Azidomethyl)-1,1-dioxido-4h-thieno[2,3-e][1,2,4]thiadiazin-3-yl]-1-(3,3-dimethylbutyl)-4-hydroxy-1-methylnaphthalen-2(1h)-oneYield 59%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of Example 185 (1 g, 2.11 mmol) in 25 mL of dichloromethane was cooled to 0° C., treated with 1,8-diazabicyclo[5.4.0]undec-7-ene (1.7 mL, 11.2 mmol) and diphenylphosphoryl azide (2.3 mL, 10.9 mmol), allowed to warm to room temp, stirred for 16 h, and concentrated onto silica gel. The crude material was chromatographed on silica gel with hexane, hexane/dichloromethane (1:1), followed by dichloromethane, and methanol/dichloromethane (1:99) to afford the title compound (610 mg, 59% yield). 1H NMR (300 MHz, DMSO-d6) δ ppm 0.39 (td, J=12.7, 3.3 Hz, 1H), 0.72 (s, 9H), 0.81 (td, J=13.1, 4.6 Hz, 1H), 1.57 (s, 3H), 2.05 (m, 1H), 2.22 (td, J=12.6, 4.6 Hz, 1H), 4.56 (s, 2H), 7.29 (m, J=8.6, 8.6 Hz, 1H), 7.54 (s, 1H), 7.74 (m, J=4.0 Hz, 2H), 8.13 (d, J=7.7 Hz, 1H), 14.09 (s, 1H); MS (APCI+) m/z 498 (M+H)+.

Workup

  1. concentrationconcentrated onto silica gel
  2. customThe crude material was chromatographed on silica gel with hexane, hexane/dichloromethane (1:1)

Sources & evidence

ORD record
ord-884d50aa64a245e78e034d46210aaba4
Source dataset
uspto-grants-2009_05
Patent number
US07538105B2

Reaction notes

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