N,N'-Dimethylethylenediamine → (E)-6-(4-chlorostyryl)-3-(4-((3,3-difluoro-1-hydroxycyclobutyl)methoxy)-3-methoxyphenyl)pyrimidin-4(3H)-one

HRID 2059880Notes

Reaction equation

CNCCNC.[Cl:7][C:8]1[CH:22]=[CH:21][C:11](/[CH:12]=[CH:13]/[C:14]2[N:19]=[CH:18][NH:17][C:16](=[O:20])[CH:15]=2)=[CH:10][CH:9]=1.Br[C:24]1[CH:38]=[CH:37][C:27]([O:28][CH2:29][C:30]2([OH:36])[CH2:33][C:32]([F:35])([F:34])[CH2:31]2)=[C:26]([O:39][CH3:40])[CH:25]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.[Cu]I>[Cl:7][C:8]1[CH:9]=[CH:10][C:11](/[CH:12]=[CH:13]/[C:14]2[N:19]=[CH:18][N:17]([C:24]3[CH:38]=[CH:37][C:27]([O:28][CH2:29][C:30]4([OH:36])[CH2:31][C:32]([F:35])([F:34])[CH2:33]4)=[C:26]([O:39][CH3:40])[CH:25]=3)[C:16](=[O:20])[CH:15]=2)=[CH:21][CH:22]=1

Participants

Conditions

Temperature: 100 °C

Procedure

N1,N2-dimethylethane-1,2-diamine (12 nL, 0.11 mmol) was added to a mixture of (E)-6-(4-chlorostyryl)pyrimidin-4(3H)-one Part B (25 mg, 0.11 mmol), 1-((4-bromo-2-methoxyphenoxy)methyl)-3,3-difluorocyclobutanol (38 mg, 0.12 mmol), potassium phosphate tribasic (68.4 mg, 0.322 mmol), and copper (I) iodide (20.5 mg, 0.11 mmol) in DMF (1 mL) and stirred at 100° C. overnight. The reaction was filtered and concentrated. The residue was purified using HPLC (Phen Luna Axia C18 5μ 10:90:0.1 to 90:10:0.1 MeOH—H2O-TFA) to afford the desired product (E)-6-(4-chlorostyryl)-3-(4-((3,3-difluoro-1-hydroxycyclobutyl)methoxy)-3-methoxyphenyl)pyrimidin-4(3H)-one J-3 (5.69 mg, 0.01 mmol, 10.93% yield) as a brown solid. LC/MS 475 (M+H)+, tR 1.00 min (method 5). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.17 (1H, s), 7.76 (1H, d), 7.53 (2H, d), 7.40 (2H, d), 7.08 (1H, d), 6.86-6.97 (3H, m), 6.48 (1H, s), 4.13 (2H, s), 3.89 (3H, s), 2.77-2.87 (4H, m)

Workup

filtrationThe reaction was filtered
concentrationconcentrated
customThe residue was purified

Sources & evidence

ORD record: ord-f7be8992449a4f45b2acfc42a0286772
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08278316B2

Reaction notes

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