(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 cyclopropylamide

HRID 1441333Notes

Reaction equation

[CH:1]1([NH:4][C:5]([C@H:7]2[CH2:11][CH2:10][CH2:9][N:8]2[C:12]2[CH:17]=[CH:16][C:15]([NH:18][C:19]([NH2:21])=[NH:20])=[CH:14][CH:13]=2)=[O:6])[CH2:3][CH2:2]1.CN(C)/[CH:24]=[CH:25]/[C:26]([C:28]1[N:32]([CH:33]([CH3:35])[CH3:34])[C:31]([CH3:36])=[N:30][CH:29]=1)=O>COCCO>[CH:1]1([NH:4][C:5]([C@H:7]2[CH2:11][CH2:10][CH2:9][N:8]2[C:12]2[CH:13]=[CH:14][C:15]([NH:18][C:19]3[N:21]=[C:26]([C:28]4[N:32]([CH:33]([CH3:35])[CH3:34])[C:31]([CH3:36])=[N:30][CH:29]=4)[CH:25]=[CH:24][N:20]=3)=[CH:16][CH:17]=2)=[O:6])[CH2:3][CH2:2]1

Participants

Conditions

Temperature: 200 °C

Procedure

(R)-1-(4-Guanidino-phenyl)-pyrrolidine-2-carboxylic acid cyclopropylamide (Method 63; 0.29 g, 1.0 mmol) and ((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, 0.68 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 (110 mg, 36%). NMR (299.954 MHz, CDCl3) 8.28 (d, 1H), 7.39 (d, 1H), 7.34 (s, 1H), 6.85-6.82 (m, 2H), 6.60-6.57 (m, 3H), 5.61 (septet, 1H), 3.96-3.92 (m, 1H), 3.62 (t, 1H), 3.19 (q, 1H), 2.76-2.67 (m, 1H), 2.56 (s, 3H), 2.30-2.22 (m, 2H), 2.07-1.84 (m, 2H), 1.47 (d, 6H), 0.78-0.70 (m, 2H), 0.45-0.38 (m, 2H); m/z 446.

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-6f92e85e034c49d9a5f3953dae374a74
Source dataset: uspto-grants-2010_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07655652B2

Reaction notes

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