Sodium Carbonate → 4-(4'-Chloro-2'-(methylthio)-4,5'-bipyrimidin-2-ylamino)benzonitrile

HRID 1397177Notes

Reaction equation

[CH3:1][S:2][C:3]1[NH:4][C:5](=O)[C:6]([C:9]2[CH:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][CH:17]=3)[N:10]=2)=[CH:7][N:8]=1.O=P(Cl)(Cl)[Cl:27].C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl>[Cl:27][C:5]1[C:6]([C:9]2[CH:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][CH:17]=3)[N:10]=2)=[CH:7][N:8]=[C:3]([S:2][CH3:1])[N:4]=1

Participants

Conditions

Temperature: 120 °C

Procedure

4-(4-(2-(Methylthio)-6-oxo-1,6-dihydropyrimidin-5-yl)pyrimidin-2-ylamino)benzonitrile (34) (700 mg, 2.081 mmol) was dissolved in POCl3 (1940 μl, 20.81 mmol), then the reaction mixture was heated at 120° C. for 3 hours. The reaction mixture was cooled to rt, then was slowly poured into an ice-cooled saturated Na2CO3 solution while stifling vigorously. The reaction mixture was then adjusted to pH 7 with additional Na2CO3 solution. DCM was added to the mixture and the aqueous layer was extracted twice with DCM. The organic extracts were combined, washed with brine, dried over sodium sulfate, then concentrated in vacuo to obtain the desired product as a bright yellow solid (428 mg, 53% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.62 (s, 3 H) 7.39 (d, J=5.05 Hz, 1 H) 7.74 (m, 2 H) 8.00 (m, J=9.09 Hz, 2 H) 8.69-8.80 (m, 1 H) 8.93 (s, 1 H) 10.42 (s, 1 H). MS (ES+): m/z=355.3 (100) [MH+]. HPLC: tR=1.57 minutes over 3 minutes. Purity: 91% [HPLC (LC/MS) at 220 nm].

Workup

temperatureThe reaction mixture was cooled to rt
extractionthe aqueous layer was extracted twice with DCM
washwashed with brine
dry with materialdried over sodium sulfate
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-cce29fea5a074178acda3be3ca86043f
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901147B2

Reaction notes

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