Triethylamine → HCID 60164948, compound

HRID 1398668Notes

Reaction equation

HRID 1398668 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][CH:20]([OH:23])[CH2:21][OH:22])[CH:5]=[CH:4][N:3]=1.[CH3:24][C:25]1[O:29][N:28]=[C:27]([C:30]([OH:34])([C:32]#[CH:33])[CH3:31])[CH:26]=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:33]#[C:32][C:30]([OH:34])([C:27]4[CH:26]=[C:25]([CH3:24])[O:29][N:28]=4)[CH3:31])[CH:15]=[CH:16][C:11]=3[N:10]=[C:9]2[O:18][CH2:19][CH:20]([OH:23])[CH2:21][OH:22])[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 582217592-(5-Methylisoxazol-3-yl)but-3-yn-2-olHCID 68181607HCID 68181607, compound

Product 1

HCID 60164948HCID 60164948, compoundYield 24.3%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 3-[[1-(2-aminopyrimidin-4-yl)-6-bromo-1H-1,3-benzodiazol-2-yl]oxy]propane-1,2-diol (80 mg, 0.21 mmol), 2-(5-methyl-1,2-oxazol-3-yl)but-3-yn-2-ol (160 mg, 1.06 mol), bis(triphenylphosphine)palladium(II) dichloride (160 mg, 0.22 mmol) and triethylamine (1 mL) in DMSO (2 mL) was stirred for 5 h at 70° C. under nitrogen atmosphere. The reaction mixture was cooled to room temperature and filtered through a frit filter. The filtrate was purified by preparative HPLC to afford 23 mg (24%) of 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]propane-1,2-diol as a white solid. 1H NMR (300 MHz, DMSO) delta 8.38 (d, J=5.4 Hz, 1H), 8.20 (s, 1H), 7.46 (d, J=8.1 Hz, 1H), 7.28 (d, J=8.1 Hz, 1H), 7.07-7.05 (m, 3H), 6.46 (s, 1H), 6.38 (s, 1H), 5.19 (d, J=5.4 Hz, 1H), 4.83-4.80 (m, 1H), 4.64 (d, J=3.6 Hz, 1H), 4.52 (d, J=6.3 Hz, 1H), 3.93 (d, J=4.5 Hz, 1H), 3.52-3.49 (m, 3H), 2.40 (s, 3H), 1.82 (s, 3H); LC-MS: m/z=451 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-ab5885ab5b7846ea9f06c1c754949204
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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