Water → HCID 57714145, compound

HRID 1163026Notes

Reaction equation

HRID 1163026 reaction equation
[O:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.[Li]CCCC.[CH3:11][C:12]([CH3:32])([CH3:31])[CH2:13][N:14]([CH2:23][C:24]1[CH:29]=[CH:28][C:27](I)=[CH:26][CH:25]=1)[C:15]1[CH:20]=[CH:19][N:18]=[C:17]([C:21]#[N:22])[N:16]=1.O>C1COCC1.[Cl-].[Cl-].[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:11][C:12]([CH3:32])([CH3:31])[CH2:13][N:14]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([C:2]2[O:1][CH:5]=[CH:4][N:3]=2)=[CH:26][CH:25]=1)[C:15]1[CH:20]=[CH:19][N:18]=[C:17]([C:21]#[N:22])[N:16]=1

Participants

8

Reactant 4

HCID 962WaterHCID 9255OxazoleHCID 44450361HCID 44450361, compoundHCID 178418339Butyllithium

Product 1

HCID 57714145HCID 57714145, compoundYield 16%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of oxazole (0.5 ml, 7.2 mmoles) in 10 ml of THF at −78° C. is added BuLi (5.23 ml, 8.0 mmoles, 1.6 M solution in hexane). After 30 min, ZnCl2 (3.0 g, 21.7 mmoles) and then a solution of 4-{(2,2-Dimethyl-propyl)-[4-iodo-benzyl]-amino}-pyrimidine-2-carbonitrile (2.9 g, 7.2 mmoles) in 10 ml of THF are added. The reaction mixture is warmed to 0° C. for 1 h. The reaction mixture is added to Pd(PPh3)4 (0.9 g, 0.8 mmoles) and heated to reflux. Water is added and is filtered through a pad of Celite which is washed with AcOEt. The organic layer is extracted with AcOEt, washed with brine, dried over magnesium sulfate and concentrated. The crude product is purified by silica gel column chromatography to give 104 mg of desired 4-[(2,2-dimethyl-propyl)-(4-oxazol-2-yl-benzyl)-amino]-pyrimidine-2-carbonitrile in 16% yield.

Workup

  1. temperatureheated to reflux
  2. filtrationis filtered through a pad of Celite which
  3. washis washed with AcOEt
  4. extractionThe organic layer is extracted with AcOEt
  5. washwashed with brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated
  8. customThe crude product is purified by silica gel column chromatography

Sources & evidence

ORD record
ord-348215da67364b8980a862494ef558b2
Source dataset
uspto-grants-2010_10
Patent number
US07820818B2

Reaction notes

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