Triethylamine → HCID 68181774, compound

HRID 1398671Notes

Reaction equation

HRID 1398671 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([O:10][CH2:11][CH:12]3[CH2:16][O:15][C:14]([CH3:18])([CH3:17])[O:13]3)[N:7]([C:19]3[CH:24]=[CH:23][N:22]=[C:21]([NH2:25])[N:20]=3)[C:6]=2[CH:26]=1.[CH3:27][C:28]1[O:32][N:31]=[C:30]([C:33]([OH:37])([C:35]#[CH:36])[CH3:34])[CH:29]=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>[NH2:25][C:21]1[N:20]=[C:19]([N:7]2[C:6]3[CH:26]=[C:2]([C:36]#[C:35][C:33]([C:30]4[CH:29]=[C:28]([CH3:27])[O:32][N:31]=4)([OH:37])[CH3:34])[CH:3]=[CH:4][C:5]=3[N:9]=[C:8]2[O:10][CH2:11][CH:12]2[CH2:16][O:15][C:14]([CH3:18])([CH3:17])[O:13]2)[CH:24]=[CH:23][N:22]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 582217592-(5-Methylisoxazol-3-yl)but-3-yn-2-olHCID 68181687HCID 68181687, compound

Product 1

HCID 68181774HCID 68181774, compoundYield 17.2%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 4-[6-bromo-2-[(2,2-dimethyl-1,3-dioxolan-4-yl)methoxy]-1H-1,3-benzodiazol-1-yl]pyrimidin-2-amine (150 mg, 0.32 mmol), 2-(5-methyl-1,2-oxazol-3-yl)but-3-yn-2-ol (300 mg, 1.98 mmol), bis(triphenylphosphine)palladium(II) dichloride (300 mg, 0.43 mmol) and triethylamine (2 mL) in dimethylsulfoxide (3 mL) was stirred for 1 h at 70° C. under a nitrogen atmosphere. The reaction mixture was cooled to room temperature then filtered through a frit filter to remove the catalyst. The filtrate was purified on a C18 column (acetonitrile/water, 5:95-80:20) to yield 27 mg (17%) of 4-[1-(2-aminopyrimidin-4-yl)-2-[(2,2-dimethyl-1,3-dioxolan-4-yl)methoxy]-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 8.38 (d, J=5.2 Hz, 1H), 8.18 (s, 1H), 7.56 (d, J=8.0 Hz, 1H), 7.28 (d, J=8.0 Hz, 1H), 7.09 (s, 2H), 7.02 (d, J=5.2 Hz, 1H), 6.44 (s, 1H), 6.38 (s, 1H), 4.69-4.54 (m, 3H), 4.11 (t, J=7.4 Hz, 1H), 3.89 (t, J=7.2 Hz, 1H), 2.41 (s, 3H), 1.81 (s, 3H), 1.32 (d, J=16 Hz, 6H); LC-MS: m/z=+491 (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 on a C18 column (acetonitrile/water, 5:95-80:20)

Sources & evidence

ORD record
ord-d414711b4aab47e984230b16b4eb8b69
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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