Dimethylacetamide → HCID 9948605, compound

HRID 895142Notes

Reaction equation

HRID 895142 reaction equation
Br[C:2]1[N:6]2[CH:7]=[N:8][C:9]([CH3:11])=[CH:10][C:5]2=[N:4][CH:3]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CC1(C)C(C)(C)OB([C:28]2[CH:29]=[C:30]([C:34]3[C:35]([C:40]#[N:41])=[CH:36][CH:37]=[CH:38][CH:39]=3)[CH:31]=[CH:32][CH:33]=2)O1.CN(C)C(=O)C>C(OCC)(=O)C.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:9]1[N:8]=[CH:7][N:6]2[C:2]([C:32]3[CH:31]=[C:30]([C:34]4[C:35]([C:40]#[N:41])=[CH:36][CH:37]=[CH:38][CH:39]=4)[CH:29]=[CH:28][CH:33]=3)=[CH:3][N:4]=[C:5]2[CH:10]=1

Participants

7

Reactant 4

HCID 31374Dimethylacetamide2×HCID 62657Potassium Phosphate, Tribasic2×HCID 112436553'-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)biphenyl-2-carbonitrile2×HCID 223857613-Bromo-7-methylimidazo[1,2-c]pyrimidine

Product 1

HCID 9948605HCID 9948605, compoundYield 49%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A stirred mixture of 3-bromo-7-methylimidazo[1,2-c]pyrimidine (0.1013 g, 0.478 mmol), dried potassium phosphate (0.2027 g, 0.955 mmol) and a 0.5 M solution of 3′-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-biphenyl-2-carbonitrile in N,N-dimethylacetamide (1.91 ml, 0.955 mmol) was degassed by evacuation and refilling with nitrogen three times. Tetrakis(triphenylphosphine)palladium(0) (28.7 mg, 0.0248 mmol) was then added and the mixture was degassed with two more evacuation-refilling cycles before heating at 80° C. under nitrogen for 45 h, adding more dried potassium phosphate (0.0503 g, 0.237 mmol), a 0.5 M solution of 3′-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)biphenyl-2-carbonitrile in N,N-dimethylacetamide (0.48 ml, 0.240 mmol) and tetrakis(triphenylphosphine)palladium(0) (8.0 mg, 0.0069 mmol) after 21 h with degassing. The mixture was diluted with ethyl acetate and filtered through glass fibre filter paper, washing solid with more ethyl acetate. The combined filtrates were washed with saturated aqueous NaCl (15 ml), and the aqueous layer was further extracted with ethyl acetate (2×25 ml). The combined organic extracts were dried (Na2SO4) and evaporated in vacuo. The residue was purified by flash chromatography (silica gel, EtOAc) to give 72.8 mg (49%) of the title compound as a yellow-brown solid: mp 119° C. (softens) (CH2Cl2-EtOAc-isohexane); 1H NMR (400 MHz, CDCl3) δ 2.57 (3H, s), 7.36 (1H, s), 7.51 (1H, td, J 7.6, 1.2 Hz), 7.57-7.72 (6H, m), 7.78 (1H, fine m), 7.82 (1H, dd, J 7.5, 1.4 Hz), 9.34 (1H, s); MS (ES+) m/z 311 [M+H]+; Anal. Found: C, 71.93; H, 4.68; N, 16.35%. Required for C20H14N4.1.4H2O: C, 71.58; H, 5.05; N, 16.70.

Workup

  1. customthe mixture was degassed with two more evacuation-refilling cycles
  2. filtrationfiltered through glass fibre filter paper
  3. washwashing solid with more ethyl acetate
  4. washThe combined filtrates were washed with saturated aqueous NaCl (15 ml)
  5. extractionthe aqueous layer was further extracted with ethyl acetate (2×25 ml)
  6. dry with materialThe combined organic extracts were dried (Na2SO4)
  7. customevaporated in vacuo
  8. customThe residue was purified by flash chromatography (silica gel, EtOAc)

Sources & evidence

ORD record
ord-230369f43df74edda291ab3077afe278
Source dataset
uspto-grants-2005_07
Patent number
US06914065B2

Reaction notes

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