Triethylamine → 1-(3-[[1-(2-aminopyrimidin-4-yl)-6-[3-hydroxy-3-(5-methyl-1,2-oxazol-3-yl)but-1-yn-1-yl]-1H-1,3-benzodiazol-2-yl]oxy]azetidin-1-yl)ethan-1-one

HRID 1398664Notes

Reaction equation

HRID 1398664 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][CH:19]2[CH2:22][N:21]([C:23](=[O:25])[CH3:24])[CH2:20]2)[CH:5]=[CH:4][N:3]=1.[CH3:26][C:27]1[O:31][N:30]=[C:29]([C:32]([OH:36])([C:34]#[CH:35])[CH3:33])[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:35]#[C:34][C:32]([OH:36])([C:29]4[CH:28]=[C:27]([CH3:26])[O:31][N:30]=4)[CH3:33])[CH:15]=[CH:16][C:11]=3[N:10]=[C:9]2[O:18][CH:19]2[CH2:22][N:21]([C:23](=[O:25])[CH3:24])[CH2:20]2)[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 582217592-(5-Methylisoxazol-3-yl)but-3-yn-2-olHCID 681817461-(3-[[1-(2-aminopyrimidin-4-yl)-6-bromo-1H-1,3-benzodiazol-2-yl]oxy]azetidin-1-yl)ethan-1-one

Product 1

HCID 681817901-(3-[[1-(2-aminopyrimidin-4-yl)-6-[3-hydroxy-3-(5-methyl-1,2-oxazol-3-yl)but-1-yn-1-yl]-1H-1,3-benzodiazol-2-yl]oxy]azetidin-1-yl)ethan-1-oneYield 21.8%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 1-(3-[[1-(2-aminopyrimidin-4-yl)-6-bromo-1H-1,3-benzodiazol-2-yl]oxy]azetidin-1-yl)ethan-1-one (130 mg, 0.29 mmol), 2-(5-methyl-1,2-oxazol-3-yl)but-3-yn-2-ol (200 mg, 1.32 mmol), bis(triphenylphosphine)palladium(II) dichloride (250 mg, 0.36 mmol) and triethylamine (1 mL) in DMSO (2 mL) was stirred under nitrogen for 5 h at 70° C. The reaction mixture was cooled to room temperature then filtered through a frit filter. The filtrate was purified by preparative HPLC to give 30 mg (21%) of 1-(3-[[1-(2-aminopyrimidin-4-yl)-6-[3-hydroxy-3-(5-methyl-1,2-oxazol-3-yl)but-1-yn-1-yl]-1H-1,3-benzodiazol-2-yl]oxy]azetidin-1-yl)ethan-1-one as a white solid: 1H NMR (400 MHz, DMSO) delta 8.41 (d, J=5.6 Hz, 1H), 8.19 (s, 1H), 7.48 (d, J=8.4 Hz, 1H), 7.29 (d, J=8.0 Hz, 1H), 7.11-7.07 (m, 3H), 6.45 (s, 1H), 6.38 (s, 1H), 5.57 (t, J=3.6 Hz, 1H), 4.61 (t, J=8.0 Hz, 1H), 4.37-4.29 (m, 2H), 4.03 (t, J=5.2 Hz, 1H), 2.41 (s, 3H), 1.81 (d, J=4.4 Hz, 6H); LC-MS: m/z=+474 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationthen filtered through a frit
  3. filtrationfilter
  4. customThe filtrate was purified by preparative HPLC

Sources & evidence

ORD record
ord-a733a5714d274cc2871c00cda70065ea
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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