4-Cyanophenylboronic acid → 1-[7-(2-Chlorophenyl)-8-(4-cyanophenyl)-2-methylpyrazolo[1,5-a][1,3,5]triazin-4-yl]-3-ethylaminoazetidine-3-carboxylic Acid Amide

HRID 2054417Notes

Reaction equation

HRID 2054417 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:27](I)=[C:11]2[N:12]=[C:13]([CH3:26])[N:14]=[C:15]([N:16]3[CH2:19][C:18]([NH:23][CH2:24][CH3:25])([C:20]([NH2:22])=[O:21])[CH2:17]3)[N:10]2[N:9]=1.[C:29]([C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1)#[N:30]>O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+].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:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:27]([C:34]2[CH:35]=[CH:36][C:31]([C:29]#[N:30])=[CH:32][CH:33]=2)=[C:11]2[N:12]=[C:13]([CH3:26])[N:14]=[C:15]([N:16]3[CH2:19][C:18]([NH:23][CH2:24][CH3:25])([C:20]([NH2:22])=[O:21])[CH2:17]3)[N:10]2[N:9]=1

Participants

6

Reactant 2

HCID 27343264-Cyanophenylboronic acidHCID 596557281-[7-(2-Chlorophenyl)-8-iodo-2-methylpyrazolo[1,5-a][1,3,5]triazin-4-yl]-3-ethylaminoazetidine-3-carboxylic Acid Amide

Product 1

HCID 596557041-[7-(2-Chlorophenyl)-8-(4-cyanophenyl)-2-methylpyrazolo[1,5-a][1,3,5]triazin-4-yl]-3-ethylaminoazetidine-3-carboxylic Acid Amide

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
68 °C

Procedure

A mixture of 1-[7-(2-chlorophenyl)-8-iodo-2-methylpyrazolo[1,5-a][1,3,5]triazin-4-yl]-3-ethylaminoazetidine-3-carboxylic acid amide (I-6A-1a; 50 mg, 0.098 mmol) and 4-cyanophenylboronic acid (22 mg, 0.15 mmol) in dioxane (0.8 ml) and 2M aqueous Na2CO3 (0.2 ml) was purged with nitrogen gas. Tetrakis(triphenylphosphine)palladium (12.5 mg, 0.01 mmol) was added and the mixture was heated at 68° C. for 4 days. After cooling to room temperature, the mixture was extracted from water with chloroform, the combined organic layers were washed with brine, dried (MgSO4), and then concentrated, in vacuo, to afford the crude product. Purification on a Combiflash® using 0.4% methanol/1% aqueous ammonium hydroxide in chloroform as eluant afforded 6A-1 (23 mg, 48%) as a solid: +ESI MS (M+1) 487.1; 1H NMR (400 MHz, CDCl3) δ 7.57 (d, J=8.7 Hz, 2H), 7.51 (d, J=8.7 Hz, 2H), 7.47-7.34 (m, 4H), 7.01 (d, J=4.6 Hz, 1H), 5.39 (d, J=4.6 Hz, 1H), 5.30 (br d, J=9.5 Hz, 1H), 4.80 (br d, J=8.7 Hz, 1H), 4.73 (br d, J=9.5 Hz, 1H), 4.18 (br d, J=8.7 Hz, 1H), 2.64 (t, J=7.0 Hz, 2H), 2.53 (s, 3H), 1.17 (t, J=7.0 Hz, 3H).

Workup

  1. customwas purged with nitrogen gas
  2. temperatureAfter cooling to room temperature
  3. extractionthe mixture was extracted from water with chloroform
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated, in vacuo

Sources & evidence

ORD record
ord-2e2986be5770471497b980a0ebe213c5
Source dataset
uspto-grants-2008_02
Patent number
US07329658B2

Reaction notes

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