2-Methyl-3-butyn-2-ol → 4-[1-(2-aminopyrimidin-4-yl)-2-[(2-methoxyethyl)amino]-1H-1,3-benzodiazol-6-yl]-2-methylbut-3-yn-2-ol

HRID 1398679Notes

Reaction equation

HRID 1398679 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:12]3[CH:13]=[C:14](Br)[CH:15]=[CH:16][C:11]=3[N:10]=[C:9]2[NH:18][CH2:19][CH2:20][O:21][CH3:22])[CH:5]=[CH:4][N:3]=1.[CH3:23][C:24]([OH:28])([C:26]#[CH:27])[CH3:25].C(N(CC)CC)C>CS(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:12]3[CH:13]=[C:14]([C:27]#[C:26][C:24]([CH3:25])([OH:28])[CH3:23])[CH:15]=[CH:16][C:11]=3[N:10]=[C:9]2[NH:18][CH2:19][CH2:20][O:21][CH3:22])[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 82582-Methyl-3-butyn-2-olHCID 8471TriethylamineHCID 681817331-(2-aminopyrimidin-4-yl)-6-bromo-N-(2-methoxyethyl)-1H-1,3-benzodiazol-2-amine

Product 1

HCID 681818384-[1-(2-aminopyrimidin-4-yl)-2-[(2-methoxyethyl)amino]-1H-1,3-benzodiazol-6-yl]-2-methylbut-3-yn-2-olYield 4.1%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 1-(2-aminopyrimidin-4-yl)-6-bromo-N-(2-methoxyethyl)-1H-1,3-benzodiazol-2-amine (120 mg, 0.33 mmol), 2-methylbut-3-yn-2-ol (277.2 mg, 3.30 mmol), bis(triphenylphosphine)palladium(II) dichloride (231.67 mg) and triethylamine (2.4 mL) in dimethylsulfoxide (1 mL) was stirred under nitrogen for 1 hr at 70° C. The reaction mixture was cooled to room temperature and the solid material was removed by filtration. The filtrate was diluted with 5 mL of water then extracted with 3×30 mL of ethyl acetate. The combined organic layers was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by preparative HPLC to give 5.0 mg (4%) of 4-[1-(2-aminopyrimidin-4-yl)-2-[(2-methoxyethyl)amino]-1H-1,3-benzodiazol-6-yl]-2-methylbut-3-yn-2-ol as a white solid: 1H NMR (300 MHz, DMSO) delta 8.43 (d, J=5.4 Hz, 1H), 8.21 (d, J=5.4 Hz, 1H), 7.47 (s, 1H), 7.25 (s, 1H), 7.16-7.12 (m, 3H), 6.91 (d, 1H), 5.40 (s, 1H), 3.63-3.57 (m, 4H), 3.35 (s, 3H), 1.47 (s, 6H); LC-MS: m/z=+367 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customthe solid material was removed by filtration
  3. additionThe filtrate was diluted with 5 mL of water
  4. extractionthen extracted with 3×30 mL of ethyl acetate
  5. dry with materialThe combined organic layers was dried over anhydrous sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-47f897a0822645f4b098ac02fed3d7ee
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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