Triethylamine → 4-[1-(2-aminopyrimidin-4-yl)-2-(2-hydroxyethoxy)-1H-1,3-benzodiazol-6-yl]-2-(5-methyl-1,2-oxazol-3-yl)but-3-yn-2-ol

HRID 1398662Notes

Reaction equation

HRID 1398662 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[O:18][CH2:19][CH2:20][OH:21])[CH:5]=[CH:4][N:3]=1.[CH3:22][C:23]1[O:27][N:26]=[C:25]([C:28]([OH:32])([C:30]#[CH:31])[CH3:29])[CH:24]=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:31]#[C:30][C:28]([C:25]4[CH:24]=[C:23]([CH3:22])[O:27][N:26]=4)([OH:32])[CH3:29])[CH:15]=[CH:16][C:11]=3[N:10]=[C:9]2[O:18][CH2:19][CH2:20][OH:21])[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 582217592-(5-Methylisoxazol-3-yl)but-3-yn-2-olHCID 681816032-[[1-(2-aminopyrimidin-4-yl)-6-bromo-1H-1,3-benzodiazol-2-yl]oxy]ethan-1-ol

Product 1

HCID 681818754-[1-(2-aminopyrimidin-4-yl)-2-(2-hydroxyethoxy)-1H-1,3-benzodiazol-6-yl]-2-(5-methyl-1,2-oxazol-3-yl)but-3-yn-2-olYield 30%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of 2-[[1-(2-aminopyrimidin-4-yl)-6-bromo-1H-1,3-benzodiazol-2-yl]oxy]ethan-1-ol (80 mg, 0.19 mmol), 2-(5-methyl-1,2-oxazol-3-yl)but-3-yn-2-ol (80 mg, 0.53 mmol), bis(triphenylphosphine)palladium(II) dichloride (20 mg, 0.03 mmol) and triethylamine (0.7 mL) in dimethylsulfoxide (3 mL) under nitrogen in a 10-mL sealed tube was irradiated with microwave radiation for 30 min at 70° C. The reaction mixture was concentrated and the crude product (80 mg) was purified by Flash-Preparative HPLC to give 24 mg (28%) of 4-[1-(2-aminopyrimidin-4-yl)-2-(2-hydroxyethoxy)-1H-1,3-benzodiazol-6-yl]-2-(5-methyl-1,2-oxazol-3-yl)but-3-yn-2-ol as a yellow solid. 1H NMR (400 MHz, DMSO-d6) delta 8.39 (d, J=5.6 Hz, 1H), 8.19 (s, 1H), 7.46 (d, J=8.0 Hz, 1H), 7.27 (d, J=8.0 Hz, 1H), 7.06 (s, 3H), 6.43 (s, 1H), 6.37 (s, 1H), 5.03 (t, J=5.2 Hz, 1H), 4.62 (s, 2H), 3.82 (d, J=4.0 Hz, 2H), 2.41 (s, 3H), 1.81 (s, 3H); LC-MS: m/z=+455 (M+H)+.

Workup

  1. customwas irradiated with microwave radiation for 30 min at 70° C
  2. concentrationThe reaction mixture was concentrated
  3. customthe crude product (80 mg) was purified by Flash-Preparative HPLC

Sources & evidence

ORD record
ord-1b1bd6ee6330410eb682578ab13e6659
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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