Potassium Carbonate → HCID 90386185, compound

HRID 2170199Notes

Reaction equation

HRID 2170199 reaction equation
Cl[C:2]1[CH:3]=[CH:4][N:5]2[C:10]=1[C:9]([NH:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=1)=[N:8][C:7]([CH:19]1[CH2:21][CH:20]1[C:22]#[N:23])=[N:6]2.[C:24]1(B(O)O)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:24]1([C:2]2[CH:3]=[CH:4][N:5]3[C:10]=2[C:9]([NH:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)=[N:8][C:7]([CH:19]2[CH2:21][CH:20]2[C:22]#[N:23])=[N:6]3)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 90386216HCID 90386216, compound

Product 1

HCID 90386185HCID 90386185, compoundYield 44.3%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of (±)-2-(5-chloro-4-((pyridin-2-ylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclopropanecarbonitrile (50.0 mg, 0.154 mmol) and phenylboronic acid (22.5 mg, 0.185 mmol) in a mixture of 1,4-dioxane (3 mL) and water (0.6 mL) was added 2-(dicyclohexylphosphino)-2′,4′,6′-triisopropylbiphenyl (14.7 mg, 0.0310 mmol), Pd(OAc)2 (3.46 mg, 0.0150 mmol) followed by K2CO3 (63.8 mg, 0.462 mmol). The resulting suspension was purged with N2 gas for 5 minutes then heated at 100° C. in a sealed tube for 12 h. The reaction mixture was allowed to cool to RT and water (10 mL) was added. The reaction mixture was extracted with EtOAc (2×25 mL) and the combined organic extracts washed with brine (10 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC (Condition B-101 as described in general methods) to afforded (±)-2-(5-phenyl-4-((pyridin-2-ylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclopropanecarbonitrile (25.0 mg, 43.9%) as white solid. LCMS Condition B-34: retention time 2.44 min, [M+1]=367.0. HPLC Condition B-5: retention time 8.52 min, purity 99.03%. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.53-1.59 (m, 2H), 2.11-2.16 (m, 1H), 2.56-2.61 (m, 1H), 4.69 (d, J=4.8 Hz, 2H), 6.71 (d, J=2.8 Hz, 1H), 7.18 (t, J=4.4 Hz, 1H), 7.27 (t, J=5.2 Hz, 1H), 7.36 (d, J=7.6 Hz, 1H), 7.42-7.53 (m, 5H), 7.73-7.78 (m, 2H), 8.35 (td, J=1.2 Hz, J=4.0 Hz, 1H).

Workup

  1. customThe resulting suspension was purged with N2 gas for 5 minutes
  2. temperatureto cool to RT
  3. additionwater (10 mL) was added
  4. extractionThe reaction mixture was extracted with EtOAc (2×25 mL)
  5. washthe combined organic extracts washed with brine (10 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by preparative HPLC (Condition B-101 as described in general methods)

Sources & evidence

ORD record
ord-78c310aa73e54dc29afad1a290fbd3e2
Source dataset
uspto-grants-2015_06
Patent number
US09050345B2

Reaction notes

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