Triethylamine → 4-[1-(2-aminopyrimidin-4-yl)-2-[(2-methoxyethyl)amino]-1H-1,3-benzodiazol-6-yl]-2-(4-methyl-1,3-thiazol-2-yl)but-3-yn-2-ol

HRID 1398680Notes

Reaction equation

HRID 1398680 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]1[N:25]=[C:26]([C:29]([OH:33])([C:31]#[CH:32])[CH3:30])[S:27][CH:28]=1.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:32]#[C:31][C:29]([C:26]4[S:27][CH:28]=[C:24]([CH3:23])[N:25]=4)([OH:33])[CH3:30])[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 8471TriethylamineHCID 681817331-(2-aminopyrimidin-4-yl)-6-bromo-N-(2-methoxyethyl)-1H-1,3-benzodiazol-2-amineHCID 866695732-(4-Methyl-1,3-thiazol-2-yl)but-3-yn-2-ol

Product 1

HCID 681817804-[1-(2-aminopyrimidin-4-yl)-2-[(2-methoxyethyl)amino]-1H-1,3-benzodiazol-6-yl]-2-(4-methyl-1,3-thiazol-2-yl)but-3-yn-2-olYield 11.8%

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 (150 mg, 0.37 mmol), 2-(4-methyl-1,3-thiazol-2-yl)but-3-yn-2-ol (137.6 mg, 0.82 mmol), bis(triphenylphosphine)palladium(II) dichloride (150 mg, 0.21 mmol) and triethylamine (0.7 mL) in dimethylsulfoxide (1 mL) under nitrogen in a 10-mL sealed tube was stirred for 1 hr at 70° C. The reaction mixture was cooled to room temperature then purified on a silica gel column (dichloromethane/methanol, 8:1) to give 19.6 mg (11%) of 4-[1-(2-aminopyrimidin-4-yl)-2-[(2-methoxyethyl)amino]-1H-1,3-benzodiazol-6-yl]-2-(4-methyl-1,3-thiazol-2-yl)but-3-yn-2-ol as yellow oil: 1H NMR (300 MHz, DMSO) delta 8.40 (d, J=5.4 Hz, 2H), 8.22 (t, J=5.0 Hz 1H), 7.49 (s, 1H), 7.27 (d, J=8.1 Hz, 1H), 7.16 (t, J=10.5 Hz, 2H), 6.91 (d, J=5.4 Hz, 1H), 6.89 (s, 1H), 6.86 (s, 1H), 3.62-3.59 (m, 4H), 3.32 (d, J=12.3 Hz, 3H), 2.35 (s, 3H), 1.85 (s, 3H); LC-MS: m/z=+450 (M+H)+.

Workup

  1. customsealed tube
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customthen purified on a silica gel column (dichloromethane/methanol, 8:1)

Sources & evidence

ORD record
ord-835e7810c7884c6bb9e1dd9324f8c511
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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