Sodium Carbonate → HCID 71282814, compound

HRID 1752433Notes

Reaction equation

[F:1][C:2]1[CH:23]=[CH:22][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10](B3OC(C)(C)C(C)(C)O3)=[CH:9][N:8]=2)=[CH:4][CH:3]=1.[NH2:24][C:25](=[O:39])[C@@H:26]([NH:28][C:29]1[N:34]=[C:33](Cl)[N:32]=[C:31]([C:36]([NH2:38])=[O:37])[CH:30]=1)[CH3:27].C([O-])([O-])=O.[Na+].[Na+]>COCCOC.CCO.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:24][C:25](=[O:39])[C@@H:26]([NH:28][C:29]1[N:34]=[C:33]([C:10]2[CH:9]=[N:8][C:7]([O:6][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:23][CH:22]=3)=[CH:12][CH:11]=2)[N:32]=[C:31]([C:36]([NH2:38])=[O:37])[CH:30]=1)[CH3:27]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 2-(4-fluorophenoxy)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)pyridine (158 mg, 0.5 mmol), (S)-6-((1-amino-1-oxopropan-2-yl)amino)-2-chloropyrimidine-4-carboxamide (121 mg, 0.5 mmol), Na2CO3 (2 M, 1 mL, 2 mmol) and Pd(PPh3)2Cl2 (20 mg, 0.025 mmol) in DME/EtOH/H2O (2 mL/1 mL/2 mL) was purged with Ar for one minute, then stirred at 100° C. for 14 hrs. The reaction mixture was then worked up with DCM. The DCM was isolated, dried over MgSO4, and removed under vacuum. The residue was subjected to silica gel flash chromatography using dichloromethane/methanol as the eluent to give (S)-6-((1-amino-1-oxopropan-2-yl)amino)-2-(6-(4-fluorophenoxy)pyridin-3-yl)pyrimidine-4-carboxamide as a gray solid (100 mg, yield 50%). NMR (DMSO-d6): 9.3 (1H, s), 8.9 (1H, m), 8.3 (1H, s), 8.05 (1H, m), 7.75 (1H, s), 7.5 (1H, s), 7.2-7.4 (4H, m), 6.95-7.15 (2H, m), 6.80 (1H, s), 4.5 (1H, m), 1.35 (3H, d, J=7.0 Hz). LC/MS: m/z=398 [M+H]+.

Workup

customwas purged with Ar for one minute
customThe DCM was isolated
dry with materialdried over MgSO4
customremoved under vacuum

Sources & evidence

ORD record: ord-81fb9a18293b40be9f59adeaa28f05f4
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09163008B2

Reaction notes

Loading…