Triethylamine → HCID 68181798, compound

HRID 1398666Notes

Reaction equation

HRID 1398666 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([O:10][CH:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)[N:7]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH2:23])[N:18]=3)[C:6]=2[CH:24]=1.[CH3:25][C:26]1[O:30][N:29]=[C:28]([C:31]([OH:35])([C:33]#[CH:34])[CH3:32])[CH:27]=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>[NH2:23][C:19]1[N:18]=[C:17]([N:7]2[C:6]3[CH:24]=[C:2]([C:34]#[C:33][C:31]([C:28]4[CH:27]=[C:26]([CH3:25])[O:30][N:29]=4)([OH:35])[CH3:32])[CH:3]=[CH:4][C:5]=3[N:9]=[C:8]2[O:10][CH:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[CH:22]=[CH:21][N:20]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 582217592-(5-Methylisoxazol-3-yl)but-3-yn-2-olHCID 68181789HCID 68181789, compound

Product 1

HCID 68181798HCID 68181798, compoundYield 24.1%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 4-[6-bromo-2-(oxan-4-yloxy)-1H-1,3-benzodiazol-1-yl]pyrimidin-2-amine (150 mg, 0.27 mmol, 70%), 2-(5-methyl-1,2-oxazol-3-yl)but-3-yn-2-ol (200 mg, 1.32 mmol), bis(triphenylphosphine)palladium(II) dichloride (220 mg, 0.31 mmol) and triethylamine (1 mL) in dimethylsulfoxide (2 mL) was stirred under nitrogen atmosphere for 5 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 30 mg (24%) of 4-[1-(2-aminopyrimidin-4-yl)-2-(oxan-4-yloxy)-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), 8.15 (s, 1H), 7.46 (d, J=8.0 Hz, 1H), 7.28-7.07 (m, 1H), 7.08 (s, 2H), 6.99 (d, J=5.6 Hz, 1H), 6.46 (s, 1H), 6.37 (s, 1H), 5.39-5.35 (m, 1H), 3.88-3.82 (m, 2H), 3.06-3.55 (m, 2H), 2.51 (s, 3H), 2.24-2.16 (m, 2H), 1.88-1.82 (m, 5H); LC-MS: m/z=+461 (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-c99c2ef2a068406ebdf12623995f33be
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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