Guanidine Hydrochloride → 4'-(Cyclopropylmethyl)-2-(methylthio)-4,5'-bipyrimidin-2'-amine

HRID 1397141Notes

Reaction equation

[CH:1]1([CH2:4][C:5](=O)/[C:6](/[C:11]2[CH:16]=[CH:15][N:14]=[C:13]([S:17][CH3:18])[N:12]=2)=[CH:7]\N(C)C)[CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].Cl.[NH2:27][C:28]([NH2:30])=[NH:29]>CN(C=O)C>[CH:1]1([CH2:4][C:5]2[C:6]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]([S:17][CH3:18])[N:12]=3)=[CH:7][N:27]=[C:28]([NH2:30])[N:29]=2)[CH2:2][CH2:3]1

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of (Z)-1-cyclopropyl-4-(dimethylamino)-3-(2-(methylthio)pyrimidin-4-yl)but-3-en-2-one (3) (2.07 g, 7.46 mmol) in DMF (62.2 ml) was added potassium carbonate (3.09 g, 22.39 mmol) and guanidine hydrochloride (1.065 g, 11.19 mmol). The resulting suspension was stirred at 120° C. After 45 minutes, the reaction was complete. The reaction mixture was concentrated in vacuo, then was taken up in EtOAc. The organic solution was washed with water, followed by brine, dried over sodium sulfate, then concentrated in vacuo. The crude residue was dried over high vacuum for 18 h to obtain the desired product as a bright orange product (2.17 g, quant. yield). MS (ES+): m/z=250.1 (50) [MH+]. HPLC: tR=1.13 min over 3 min. Purity: 100% [HPLC (LC/MS) at 220 nm]. 1H NMR (400 MHz, DMSO-d6) d ppm 0.06-0.13 (m, 2H) 0.33-0.41 (m, 2 H) 0.96-1.11 (m, 1 H) 2.52-2.57 (m, 3 H) 2.79 (d, J=7.07 Hz, 2 H) 7.03 (s, 2 H) 7.39 (d, J=5.56 Hz, 1 H) 8.44 (s, 1 H) 8.60 (d, J=5.56 Hz, 1 H).

Workup

concentrationThe reaction mixture was concentrated in vacuo
washThe organic solution was washed with water
dry with materialdried over sodium sulfate
concentrationconcentrated in vacuo
dry with materialThe crude residue was dried over high vacuum for 18 h

Sources & evidence

ORD record: ord-c5929c955a3e459892d2b3fa541692e8
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901147B2

Reaction notes

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