Dimethylformamide → HCID 11339645, compound

HRID 915860Notes

Reaction equation

HRID 915860 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:23]([C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=2)=[C:11]2[N:12]=[C:13]([CH3:22])[N:14]=[C:15]([O:16][CH2:17][C:18]([F:21])([F:20])[CH3:19])[C:10]2=[N:9]1.[CH3:31][N:32](C=O)C>[C-]#N.[C-]#N.[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>[Cl:30][C:27]1[CH:28]=[CH:29][C:24]([C:23]2[N:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[C:31]#[N:32])[N:9]=[C:10]3[C:15]([O:16][CH2:17][C:18]([F:20])([F:21])[CH3:19])=[N:14][C:13]([CH3:22])=[N:12][C:11]=23)=[CH:25][CH:26]=1

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 11466051HCID 11466051, compound

Product 1

HCID 11339645HCID 11339645, compound

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
200 °C

Procedure

A mixture of 2-(2-bromophenyl)-3-(4-chlorophenyl)-7-(2,2-difluoropropoxy)-5-methyl-2H-pyrazolo[4,3-d]pyrimidine (10A-7, 50 mg, 0.1 mmol), Zn(CN)2(20 mg, 0.17 mmol), Pd(PPh3)4 (15 mg, 0.01 mmol) in DMF (1 ml) was heated in a microwave apparatus (Emrys Optimizer, Personal Chemistry) at 200° C. for 3 minutes. The reaction mixture was quenched with saturated aqueous NaCl and extracted with ethyl acetate (2×). The combined organic extracts were dried and concentrated under vacuum. The crude residue was purified via HPLC (Shimadzu) using a solvent gradient of 30% CH3CN/hexanes to 100% CH3CN to give the desired product, 2-[3-(4-chlorophenyl)-7-(2,2-difluoropropoxy)-5-methylpyrazolo[4,3-d]pyrimidin-2-yl]-benzonitrile (11A-1), as a colorless solid (25 mg): MS (M+1)+440.0; 1H NMR (400 MHz, CDCl3) δ 7.80-7.64 (m, 4H), 7.40-7.26 (m, 4H), 4.8 (t, J=11.6 Hz, 2H), 2.7 (s, 3H), 1.79 (t, J=18.67 Hz, 3H).

Workup

  1. customThe reaction mixture was quenched with saturated aqueous NaCl
  2. extractionextracted with ethyl acetate (2×)
  3. customThe combined organic extracts were dried
  4. concentrationconcentrated under vacuum
  5. customThe crude residue was purified via HPLC (Shimadzu)

Sources & evidence

ORD record
ord-1c52aa518910425781621d1efcc2d247
Source dataset
uspto-grants-2007_09
Patent number
US07268133B2

Reaction notes

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