Dimethylformamide → HCID 86731426, compound

HRID 2277335Notes

Reaction equation

HRID 2277335 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[O:16][C:17]3[N:18]=[C:19](Cl)[N:20]=[CH:21][C:22]=3[N:23]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:25][C@H:26]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[C:27]#[CH:28].C(N(CC)CC)C.CN(C=O)C>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.[Cu]I.O.C1(C)C=CC=CC=1>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[O:16][C:17]3[N:18]=[C:19]([C:28]#[C:27][C@@H:26]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH3:25])[N:20]=[CH:21][C:22]=3[N:23]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 8471Triethylamine2×HCID 10986677tert-Butyl (2S)-but-3-yn-2-ylcarbamate2×HCID 86731425HCID 86731425, compound2×

Product 1

HCID 86731426HCID 86731426, compound

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 178418476HCID 178418476, compoundCatalyst2×HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A mixture of 4-(benzyloxy)benzoic acid (1.04 g) and phosphorus oxychloride (12.2 mL) was stirred at room temperature for 5 min, and 2,4-dichloropyrimidin-5-amine (500 mg) was added thereto, and the obtained mixture was stirred at 100° C. for 2 hr. The reaction mixture was added to 1M aqueous sodium hydroxide solution at 0° C., and the precipitate was collected by filtration, and dissolved in THF and ethyl acetate. The obtained solution was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give 2-(4-(benzyloxy)phenyl)-5-chloro[1,3]oxazolo[5,4-d]pyrimidine (3.07 g) as a mixture with impurity. A mixture of 2-(4-(benzyloxy)phenyl)-5-chloro[1,3]oxazolo[5,4-d]pyrimidine (100 mg, a mixture with impurity), tert-butyl (2S)-but-3-yn-2-ylcarbamate (50.1 mg), dichlorobis(triphenylphosphine)palladium(II) (10.4 mg), copper(I) iodide (5.64 mg), triethylamine (0.041 mL) and DMF (2 mL) was stirred at 100° C. for 6 hr under an argon atmosphere. In another reaction container, A mixture of 2-(4-(benzyloxy)phenyl)-5-chloro[1,3]oxazolo[5,4-d]pyrimidine (100 mg, a mixture with impurity), tert-butyl (2S)-but-3-yn-2-ylcarbamate (50.1 mg), dichlorobis(triphenylphosphine)palladium(II) (10.4 mg), copper(I) iodide (5.64 mg), triethylamine (0.041 mL) and toluene (2 mL) was stirred at 100° C. for 6 hr under an argon atmosphere. The two reaction mixtures were combined, water was added thereto, and the mixture was extracted with ethyl acetate. The combined organic layer were washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (44.4 mg).

Workup

  1. customThe two reaction mixtures
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe combined organic layer were washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-e60941bd1a1c462b9b31441e9e351c01
Source dataset
uspto-grants-2015_09
Patent number
US09133129B2

Reaction notes

Loading…