Dimethylformamide → HCID 10183232, compound

HRID 861135Notes

Reaction equation

HRID 861135 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2[C:22]([C:23]3[CH:28]=[CH:27][N:26]=[C:25]([NH:29][CH:30]4[CH2:34][CH2:33][CH2:32][CH2:31]4)[N:24]=3)=[C:11]3[CH:12]=[CH:13][CH:14]=[C:15]([NH:16][CH:17]4[CH2:21][CH2:20][CH2:19][CH2:18]4)[N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.C(OCC)(=O)C.[CH3:41][N:42](C)C=O>[C-]#N.[Zn+2].[C-]#N.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH:17]1([NH:16][C:15]2[N:10]3[N:9]=[C:8]([C:4]4[CH:3]=[C:2]([CH:7]=[CH:6][CH:5]=4)[C:41]#[N:42])[C:22]([C:23]4[CH:28]=[CH:27][N:26]=[C:25]([NH:29][CH:30]5[CH2:34][CH2:33][CH2:32][CH2:31]5)[N:24]=4)=[C:11]3[CH:12]=[CH:13][CH:14]=2)[CH2:21][CH2:20][CH2:19][CH2:18]1

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 8857Ethyl AcetateHCID 10142612HCID 10142612, compound

Product 1

HCID 10183232HCID 10183232, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Catalyst

Procedure

To a solution of 2-(3-bromophenyl)-N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]pyrazolo[1,5-a]pyridin-7-amine (500 mg, 0.97 mmol) in N,N-dimethylformamide (25 mL) was added zinc cyanide (68 mg, 0.58 mmol), tris(dibenzylidineacetone)bipalladium(0) (888 mg, 0.97 mmol) and 1,1′-bis(diphenylphosphino) ferrocene (1.29 g, 2.3 mmol). The resultant mixture was heated at 120° C. for 20 hours. After cooling to room temperature, ethyl acetate was added to the reaction mixture. The organic phase was washed with water, brine and dried over magnesium sulfate. Filtration and concentration, followed by purification with flash chromatography (40:60 ethyl acetate:hexanes) gave 3-{7-(cyclopentylamino)-3-[2-(cyclopentylamino)-4-pyrimidinyl]pyrazolo[1,5-a]pyridin-2-yl}benzonitrile (0.19 g, yield 42%) as a yellow foam. 1H NMR (CDCl3): δ 8.07 (m, 2H), 7.89 (d, 1H), 7.70 (d, 1H), 7.62 (d, 1H), 7.52 (t, 1H), 7.33 (t, 1H), 6.33 (d, 1H), 6.06 (d, 1H), 6.00 (d, 1H), 5.16 (d, 1H), 4.25 (m, 1H), 4.02 (m, 1H), 2.15 (m, 2H), 2.03 (m, 2H), 1.85–1.51 (m, 12H). MS m/z 464 (M+1).

Workup

  1. washThe organic phase was washed with water, brine
  2. dry with materialdried over magnesium sulfate
  3. filtrationFiltration and concentration
  4. customfollowed by purification with flash chromatography (40:60 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-b1a2d302ba5b4e179b14ddb40b133f69
Source dataset
uspto-grants-2006_12
Patent number
US07153855B2

Reaction notes

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