(E)-3-(Dimethylamino)-1-(1-isopropyl-2-methyl-1H-imidazol-5-yl)prop-2-en-1-one → (R)-1-{4-[4-(3-Isopropyl-2-methyl-3H-imidazol-4-yl)-pyrimidin-2-ylamino]-phenyl}-pyrrolidine-2-carboxylic acid methylamide

HRID 1441342Notes

Reaction equation

[CH3:1][NH:2][C:3]([C@H:5]1[CH2:9][CH2:8][CH2:7][N:6]1[C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]([NH2:19])=[NH:18])=[CH:12][CH:11]=1)=[O:4].CN(C)/[CH:22]=[CH:23]/[C:24]([C:26]1[N:30]([CH:31]([CH3:33])[CH3:32])[C:29]([CH3:34])=[N:28][CH:27]=1)=O>COCCO>[CH3:1][NH:2][C:3]([C@H:5]1[CH2:9][CH2:8][CH2:7][N:6]1[C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]2[N:19]=[C:24]([C:26]3[N:30]([CH:31]([CH3:33])[CH3:32])[C:29]([CH3:34])=[N:28][CH:27]=3)[CH:23]=[CH:22][N:18]=2)=[CH:12][CH:11]=1)=[O:4]

Participants

Conditions

Temperature: 200 °C

Procedure

(R)-1-(4-Guanidino-phenyl)-pyrrolidine-2-carboxylic acid methylamide (Method 59; 0.27 g, 1.0 mmol) and of (2E)-3-(dimethylamino)-1-(1-isopropyl-2-methyl-1H-imidazol-5-yl)prop-2-en-1-one, (Method 24 of WO 03/076436; 0.15 g, 0.0.68 mmol) were added to 2-methoxyethanol (4 ml) and heated at 200° C. for 2 hours in the microwave. The solvent was removed in vacuo and the gum was carefully chromatographed eluting with DCM, 1% MeOH/DCM, 2% MeOH/DCM and finally 3% MeOH/DCM to yield a yellow solid (101 mg, 35%). NMR (400.132 MHz, CDCl3) 8.28 (d, 1H), 7.39 (d, 2H), 7.34 (s, 1H), 6.89 (s, 1H), 6.83 (d, 1H), 6.61-6.57 (m, 3H), 5.62 (septet, 1H), 3.99 (t, 1H), 3.65 (t, 1H), 3.24-3.17 (m, 1H), 2.80 (d, 3H), 2.55 (s, 3H), 2.29-2.24 (m, 2H), 2.06-1.89 (m, 2H), 1.46 (d, 6H); m/z 420.

Workup

customThe solvent was removed in vacuo
customthe gum was carefully chromatographed
washeluting with DCM, 1% MeOH/DCM, 2% MeOH/DCM and finally 3% MeOH/DCM

Sources & evidence

ORD record: ord-7ccb3b4585cc497cb8f1de2e9dbbc1c6
Source dataset: uspto-grants-2010_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07655652B2

Reaction notes

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