Triethylamine → HCID 60163662, compound

HRID 1398678Notes

Reaction equation

HRID 1398678 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]([CH2:23][CH2:24][OH:25])[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]([C:29]4[CH:28]=[C:27]([CH3:26])[O:31][N:30]=4)([OH:36])[CH3:33])[CH:15]=[CH:16][C:11]=3[N:10]=[C:9]2[O:18][CH:19]2[CH2:22][N:21]([CH2:23][CH2:24][OH:25])[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 68181617HCID 68181617, compound

Product 1

HCID 60163662HCID 60163662, compoundYield 7.4%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 2-(3-[[1-(2-aminopyrimidin-4-yl)-6-bromo-1H-1,3-benzodiazol-2-yl]oxy]azetidin-1-yl)ethan-1-ol (80 mg, 0.20 mmol), 2-(5-methyl-1,2-oxazol-3-yl)but-3-yn-2-ol (160 mg, 1.06 mmol), bis(triphenylphosphine)palladium(II) dichloride (160 mg, 0.23 mmol) and triethylamine (1 mL) in dimethylsulfoxide (2 mL) was stirred under nitrogen for 2 hr at 70° C. The reaction mixture was cooled to room temperature then filtered through a frit filter to remove the catalyst. The filtrate was purified by preparative HPLC to give 7 mg (7%) of 4-[1-(2-aminopyrimidin-4-yl)-2-[[1-(2-hydroxyethyl)azetidin-3-yl]oxy]-1H-1,3-benzodiazol-6-yl]-2-(5-methyl-1,2-oxazol-3-yl)but-3-yn-2-ol as a white solid: 1H NMR (400 MHz, DMSO) delta 8.41 (d, J=5.6 Hz, 1H), 8.17 (s, 1H), 7.46 (d, J=8.4 Hz, 1H), 7.27 (d, J=8.4 Hz, 1H), 7.10 (s, 2H), 7.01 (d, J=5.6 Hz, 1H), 6.45 (s, 1H), 6.37 (s, 1H), 5.37 (t, J=5.2 Hz, 1H), 4.44 (t, J=5.4 Hz, 1H), 3.75 (t, J=7.2 Hz, 2H), 3.41 (t, J=6.0 Hz, 2H), 3.28 (t, J=6.8 Hz, 2H), 2.57 (s, 2H), 2.41 (s, 3H), 1.81 (s, 3H); LC-MS: m/z=+476 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-77d3aa3f40f8443c82a6440b7b371367
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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