4-Fluoroaniline → HCID 90409046, compound

HRID 1521684Notes

Reaction equation

HRID 1521684 reaction equation
[C:1]([C:4]1[CH:27]=[CH:26][C:7]([CH2:8][N:9]2[C:24](Cl)=[C:12]3[C:13](=[O:23])[N:14]([CH3:22])[C:15]4[N:16]([CH2:17][C:18]([CH3:21])([CH3:20])[N:19]=4)[C:11]3=[N:10]2)=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[F:28][C:29]1[CH:34]=[CH:33][C:32]([NH2:35])=[CH:31][CH:30]=1.[C:36](=O)([O-:38])[O-:37].[K+].[K+]>C(O)(CC)(C)C.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].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[C:1]([C:4]1[CH:27]=[CH:26][C:7]([CH2:8][N:9]2[C:24]([NH:35][C:32]3[CH:33]=[CH:34][C:29]([F:28])=[CH:30][CH:31]=3)=[C:12]3[C:13](=[O:23])[N:14]([CH3:22])[C:15]4[N:16]([CH2:17][C:18]([CH3:21])([CH3:20])[N:19]=4)[C:11]3=[N:10]2)=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[CH:36]([O-:38])=[O:37]

Participants

8

Reactant 3

HCID 97314-FluoroanilineHCID 11430Potassium CarbonateHCID 90408179HCID 90408179, compound

Product 2

HCID 283FormateYield 54%HCID 90409046HCID 90409046, compoundYield 59.7%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 64052-Methyl-2-butanolSolvent

Conditions

Temperature
110 °C

Procedure

7,8-Dihydro-2-(4-acetylbenzyl)-3-chloro-5,7,7-trimethyl-[2H]-imidazo-[1,2-a]pyrazolo[4,3-e]pyrimidin-4(5H)-one (150 mg, 0.389 mmol), 4-fluorobenzenamine (41 μL, 0.428 mmol) and potassium carbonate (107 mg, 0.775 mmol) in tert-amyl alcohol (1.3 mL) are degassed with argon and then Xantphos (9.0 mg, 0.016 mmol) and Pd2(dba)3 (7.13 mg, 0.0078 mmol) are added. The suspension is degassed again, and then heated to 110° C. The reaction mixture is stirred at 110° C. under argon for 24 h. After routine workup, the crude mixture is purified with a semi-preparative HPLC to give 107 mg of the final product as a formate salt (HPLC purity: 96%; yield: 54%). 1H NMR (500 MHz, Chloroform-d) δ 8.20 (s, 1H), 7.84 (d, J=8.3 Hz, 2H), 7.06-7.00 (m, 3H), 6.99-6.92 (m, 2H), 6.92-6.86 (m, 2H), 4.91 (s, 2H), 3.77 (s, 2H), 3.37 (s, 3H), 2.57 (s, 3H), 1.48 (s, 6H). MS (ESI) m/z 461.2 [M+H]+.

Workup

  1. customThe suspension is degassed again
  2. customAfter routine workup, the crude mixture is purified with a semi-preparative HPLC

Sources & evidence

ORD record
ord-35556c0d55a84701bc44e3e210235b68
Source dataset
uspto-grants-2015_07
Patent number
US09073936B2

Reaction notes

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