HCID 59805694, compound → HCID 136347364, compound

HRID 601386Notes

Reaction equation

HRID 601386 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[CH:4][C:3]=1[S:16]([NH2:19])(=[O:18])=[O:17].CS[C:22](SC)=[C:23]1[C:32](=[O:33])[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[N:25]([NH:34][CH2:35][CH:36]2[CH2:38][CH2:37]2)[C:24]1=[O:39]>O1CCOCC1>[CH:36]1([CH2:35][NH:34][N:25]2[C:26]3[C:31](=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:32]([OH:33])=[C:23]([C:22]3[NH:1][C:2]4[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:13])([CH3:14])[CH3:12])=[CH:4][C:3]=4[S:16](=[O:17])(=[O:18])[N:19]=3)[C:24]2=[O:39])[CH2:37][CH2:38]1

Participants

4

Reactant 2

HCID 59805694HCID 59805694, compoundHCID 670636773-[bis(methylthio)methylene]-1-[(cyclopropylmethyl)amino]quinoline-2,4(1H,3H)-dione

Product 1

HCID 136347364HCID 136347364, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of the product of Example 414A (78.1 mg, 0.272 mmol) and the product of Example 353B (91.0 mg, 0.272 mmol) in anhydrous dioxane (2.7 mL) was heated under reflux for 3 h. The reaction mixture was then cooled to 25° C. and concentrated under reduced pressure to yield an oily solid. The solid was triturated with methanol to yield the title compound (72.5 mg, 51%). 1H NMR (300 MHz, DMSO-d6) δ 0.14 (d, J=4.04 Hz, 2 H) 0.42 (m, 2 H) 1.00 (m, 1 H) 1.51 (s, 9 H) 2.85 (bd, J=4.78 Hz, 2 H) 6.45 (bs, 1 H) 7.44 (t, J=7.54 Hz, 1 H) 7.62 (d, J=8.82 Hz, 1 H) 7.69 (dd, J=8.82, 2.20 Hz, 1 H) 7.89 (m, J=7.91, 7.91 Hz, 1 H) 8.10 (d, J=8.46 Hz, 1 H) 8.17 (m, 2 H) 9.93 (s, 1 H) 14.08 (s, 1 H) 15.15 (d, J=4.78 Hz, 1 H). MS (ESI−) m/z 524.0 (M−H)−. The sodium salt of the compound was prepared by reacting example 414B (3.9 mg, 0.0074 mmol) with 1 N sodium hydroxide solution (0.0074 mL, 0.0074 mmol) in 0.5 mL water and 0.5 mL tetrahydrofuran at room temperature for 1.2 h. The reaction mixture was then evaporated under a stream of nitrogen to provide the sodium salt (4.1 mg, 100% yield). 1H NMR (300 MHz, DMSO-d6) δ 0.20 (m, J=5.52 Hz, 2 H) 0.46 (d, J=8.82 Hz, 2 H) 1.00 (m, 1 H) 1.50 (s, 9 H) 3.30 (m, 2 H) 5.96 (t, J=6.25 Hz, 1 H) 7.06 (t, J=7.17 Hz, 1 H) 7.20 (d, J=9.19 Hz, 1 H) 7.52 (m, 2 H) 7.67 (d, J=8.82 Hz, 1 H) 7.90 (s, 1 H) 8.06 (d, J=7.35 Hz, 1 H) 9.60 (s, 1 H) 16.22 (s, 1 H). MS (ESI+) m/z 543.1 (M+H+H2O-Na)+, 526.1 (M−Na)+, (ESI−) m/z 524.1 (M−H)−.

Workup

  1. temperatureunder reflux for 3 h
  2. concentrationconcentrated under reduced pressure
  3. customto yield an oily solid
  4. customThe solid was triturated with methanol

Sources & evidence

ORD record
ord-499985f777e84a24946a9f9c8e9b0c67
Source dataset
uspto-grants-2011_03
Patent number
US07902203B2

Reaction notes

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