1,4-Dioxane → 4-{2-Amino-6-[(2R)-2-ethyl-1-pyrrolidinyl]-4-pyrimidinyl}-2-fluorobenzonitrile

HRID 2367226Notes

Reaction equation

Cl[C:2]1[CH:7]=[C:6]([N:8]2[CH2:12][CH2:11][CH2:10][C@H:9]2[CH2:13][CH3:14])[N:5]=[C:4]([NH2:15])[N:3]=1.[C:16]([C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][C:19]=1[F:27])#[N:17].O1CCOCC1.C([O-])(O)=O.[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.CCOC(C)=O>[NH2:15][C:4]1[N:3]=[C:2]([C:21]2[CH:22]=[CH:23][C:18]([C:16]#[N:17])=[C:19]([F:27])[CH:20]=2)[CH:7]=[C:6]([N:8]2[CH2:12][CH2:11][CH2:10][C@H:9]2[CH2:13][CH3:14])[N:5]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To 4-chloro-6-[(2R)-2-ethyl-1-pyrrolidinyl]-2-pyrimidinamine (40 mg, 0.176 mmol) and (4-cyano-3-fluorophenyl)boronic acid (29.1 mg, 0.176 mmol) was added 1,4-dioxane (3 mL) followed by sat. aq. NaHCO3 (0.5 mL), and the mixture was purged with N2 for 10 minutes into a sealable tube. Pd(Ph3P)4 (20.4 mg, 0.018 mmol) was added, the tube was sealed, and the reaction mixture was stirred overnight at 100° C. The mixture was poured onto water and EtOAc. The organic layer was separated, washed with brine, dried (MgSO4), filtered and concentrated. Flash chromatography on SiO2 (gradient: 100° ACHCl3 to 95:5:0.5 CHCl3:CH3OH:NH4OH) afforded the title compound (52 mg) as a solid. LC-MS (ES) m/z=312 [M+H]+.

Workup

customthe mixture was purged with N2 for 10 minutes into a sealable tube
customthe tube was sealed
customThe organic layer was separated
washwashed with brine
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-8bc8eb5798fe48c5a04c91f2d148c853
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08697685B2

Reaction notes

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