HCID 118235731, compound → HCID 118235817, compound

HRID 626993Notes

Reaction equation

HRID 626993 reaction equation
[F:1][CH:2]([F:38])[O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:10][C:11]1[N:15]2[CH:16]=[C:17]([C:21]3[CH:22]=[N:23][C:24]([N:27]4[CH2:32][CH2:31][C:30]([CH3:36])([C:33]([OH:35])=[O:34])[CH2:29][CH2:28]4)=[N:25][CH:26]=3)[C:18]([F:20])=[CH:19][C:14]2=[N:13][C:12]=1[CH3:37]>[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.CS(C)=O.CCOC(C)=O>[F:38][CH:2]([F:1])[O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:10][C:11]1[N:15]2[CH:16]=[C:17]([C:21]3[CH:26]=[N:25][C:24]([N:27]4[CH2:32][CH2:31][C:30]([CH3:36])([C:33]([O:35][CH2:9][CH2:4][CH2:5][CH3:6])=[O:34])[CH2:29][CH2:28]4)=[N:23][CH:22]=3)[C:18]([F:20])=[CH:19][C:14]2=[N:13][C:12]=1[CH3:37]

Participants

5

Reactant 1

HCID 118235731HCID 118235731, compound

Product 1

HCID 118235817HCID 118235817, compoundYield 81.4%

Reagents, catalysts & solvents 3

HCID 70681Tetrabutylammonium ChlorideCatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
180 °C

Procedure

A suspension of the sodium salt of Example 46 (207 mg, 0.38 mmol) and tetra-n-butylammonium chloride (42 mg, 1.5 mmol) in DMSO (2.5 mL) was heated under microwave irradiation, in a sealed tube, to 180° C. for 10 minutes. The reaction mixture was diluted with EtOAc (30 mL), and washed with HCl (1M, 20 mL), water (2×20 mL) and brine (20 mL), then the organic layers were dried over MgSO4 and the solvent was removed. The resulting crude yellow gum (270 mg) was purified by uv-directed preparative HPLC (pH 10 method eluting with 50-65% solvent B) to give the title compound (90 mg, 41%) as a colourless gum. δH (400 MHz, CD3OD) 8.39 (s 2H), 8.10 (d, 1H, J 7.3 Hz), 7.32-7.26 (m 2H), 7.21 (m, 1H), 7.16 (t, 1H, J 7.7 Hz), 7.10-7.08 (m, 1H), 6.92 (t, 1H, J 74 Hz), 4.42 (t, 2H, J 4.0 Hz), 4.38 (s, 2H), 4.18 (t, 2H, J 6.4 Hz), 3.40-3.37 (m, 2H), 2.42 (s, 3H), 2.17 (d, 2H, J 13.6 Hz), 1.69 (m, 2H), 1.51-1.42 (m, 4H), 1.26 (s, 3H), 0.99 (t, 3H, J 7.3 Hz). HPLC-MS (pH 10): MH+ m/z 582.8, RT 3.04 minutes.

Workup

  1. washwashed with HCl (1M, 20 mL), water (2×20 mL) and brine (20 mL)
  2. dry with materialthe organic layers were dried over MgSO4
  3. customthe solvent was removed
  4. customThe resulting crude yellow gum (270 mg) was purified by uv-directed preparative HPLC (pH 10 method eluting with 50-65% solvent B)

Sources & evidence

ORD record
ord-8145e5e9c2214a4891b43fcbce176fd9
Source dataset
uspto-grants-2016_04
Patent number
US09309243B2

Reaction notes

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