2-Aminothiophenol → trans-2-(2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)cyclopropyl)benzo[d]thiazole

HRID 1498816Notes

Reaction equation

HRID 1498816 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[SH:8].C[Al](C)C.[CH3:13][C:14]1[N:18]=[C:17]([CH3:19])[N:16]([C:20]2[N:25]=[C:24]([CH3:26])[N:23]=[C:22]([C@@H:27]3[CH2:29][C@H:28]3[C:30](OCC)=O)[CH:21]=2)[N:15]=1>C1(C)C=CC=CC=1>[CH3:13][C:14]1[N:18]=[C:17]([CH3:19])[N:16]([C:20]2[N:25]=[C:24]([CH3:26])[N:23]=[C:22]([C@@H:27]3[CH2:29][C@H:28]3[C:30]3[S:8][C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=4[N:1]=3)[CH:21]=2)[N:15]=1

Participants

5

Reactant 3

HCID 87132-AminothiophenolHCID 16682925TrimethylaluminumHCID 86732076ethyl trans-2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)cyclopropanecarboxylate

Product 1

HCID 86732077trans-2-(2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)cyclopropyl)benzo[d]thiazole

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
130 °C

Procedure

To 2-aminobenzenethiol (24.0 mg, 0.19 mmol, 1.1 eq.) dissolved in anhydrous toluene (5.0 mL) was added trimethylaluminium (2.0 M in toluene, 0.25 mL, 0.50 mmol, 3.0 eq.) under nitrogen at 0° C. dropwise. The reaction was stirred at a temperature between 10° C. to 20° C. for 30 minutes followed by the addition of ethyl trans-2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)cyclopropanecarboxylate (2-1) (50.0 mg, 0.165 mmol, 1.0 eq.) and the reaction was heated to 130° C. for 24 hours. The reaction was cooled to room temperature and quenched with saturated sodium bicarbonate (10 mL) and extracted with ethyl acetate (3×20 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrate to dryness. The resulting residue was purified by silica gel column chromatography (10-40% ethyl acetate in toluene) to afford trans-2-(2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)cyclopropyl)benzo[d]thiazole (2-2) as a yellow glue. 1H NMR (300 MHz, CDCl3) δ 7.92 (br d, 1H, J=8.0 Hz), 7.81 (m, 1H), 7.64 (br s, 1H), 7.45 (m, 1H), 7.34 (m, 1H), 3.11 (ddd, 1H, J=9.7, 5.9, 3.9 Hz), 2.92-2.83 (m, 1H), 2.89 (s, 3H), 2.66 (s, 3H), 2.39 (s, 3H), 2.13-1.97 (m, 2H). LRMS m/z (M+H+) 363 found, 363 required.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customquenched with saturated sodium bicarbonate (10 mL)
  3. extractionextracted with ethyl acetate (3×20 mL)
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrate to dryness
  7. customThe resulting residue was purified by silica gel column chromatography (10-40% ethyl acetate in toluene)

Sources & evidence

ORD record
ord-13189fab942c4b4c8ab3e2ddf6f53c31
Source dataset
uspto-grants-2015_12
Patent number
US09200001B2

Reaction notes

Loading…