2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → 2-{[5-Amino-4-(2-dimethylaminoethyl-methylamino)-2-methoxyphenyl]-amino}-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidine-5-carbonitrile

HRID 1842775Notes

Reaction equation

HRID 1842775 reaction equation
Cl[C:2]1[C:3]([C:25]2[CH:26]=[N:27][N:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=23)=[N:4][C:5]([NH:8][C:9]2[CH:10]=[C:11]([NH2:24])[C:12]([N:17]([CH2:19][CH2:20][N:21]([CH3:23])[CH3:22])[CH3:18])=[CH:13][C:14]=2[O:15][CH3:16])=[N:6][CH:7]=1.[C:34]([Zn]C#N)#[N:35].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>CC(N(C)C)=O.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].[Zn]>[NH2:24][C:11]1[C:12]([N:17]([CH2:19][CH2:20][N:21]([CH3:23])[CH3:22])[CH3:18])=[CH:13][C:14]([O:15][CH3:16])=[C:9]([NH:8][C:5]2[N:4]=[C:3]([C:25]3[CH:26]=[N:27][N:28]4[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=34)[C:2]([C:34]#[N:35])=[CH:7][N:6]=2)[CH:10]=1

Participants

8

Reactant 3

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86677330N4-(5-Chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)-N1-(2-dimethylaminoethyl)-5-methoxy-N1-methylbenzene-1,2,4-triamine2×HCID 178514179HCID 178514179, compound

Product 1

HCID 866772852-{[5-Amino-4-(2-dimethylaminoethyl-methylamino)-2-methoxyphenyl]-amino}-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidine-5-carbonitrileYield 52.5%

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
95 °C

Procedure

N4-(5-Chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)-N1-(2-dimethylaminoethyl)-5-methoxy-N1-methylbenzene-1,2,4-triamine (Intermediate 33, 120 mg, 0.26 mmol), dicyanozinc (18.11 mg, 0.15 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (24.50 mg, 0.05 mmol), tris(dibenzylideneacetone)dipalladium(0) (23.5 mg, 0.03 mmol) and zinc powder (1.681 mg, 0.03 mmol) were suspended in degassed DMA (1.1 mL) and sealed into a microwave tube. The mixture was then heated to 95° C. for 1 h in a microwave. The cooled mixture was then diluted with EtOAc (50 mL) and washed with sat. NaHCO3 (20 mL), water (20 mL), and sat. brine (10 mL). The organic solution was then concentrated in vacuo. Purification by FCC, eluting with 0-20% CH3OH in CH2Cl2 gave the title compound (36 mg, 31%) as a yellow gum; 1H NMR: (CDCl3) 2.41 (6H, s), 2.60 (2H, s), 2.72 (3H, s), 3.07 (2H, t), 3.86 (3H, s), 6.72 (1H, s), 7.02 (1H, t), 7.41-7.53 (1H, m), 7.80 (2H, d), 8.60 (2H, d), 8.70 (1H, d), 9.09 (1H, s); m/z: ES+ MH+ 458.30.

Workup

  1. customsealed into a microwave tube
  2. washwashed with sat. NaHCO3 (20 mL), water (20 mL), and sat. brine (10 mL)
  3. concentrationThe organic solution was then concentrated in vacuo
  4. customPurification by FCC
  5. washeluting with 0-20% CH3OH in CH2Cl2

Sources & evidence

ORD record
ord-7c5c083704804cfbbfc4efe5c9b8c5de
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

Loading…