(2Z)-3-(dimethylamino)-2-fluoro-1-(1-isopropyl-2-methyl-1H-imidazol-5-yl)prop-2-en-1-one → (R)-1-{4-[5-Fluoro-4-(3-isopropyl-2-methyl-3H-imidazol-4-yl)-pyrimidin-2-ylamino]-phenyl}-pyrrolidine-2-carboxylic acid cylopropylamide

HRID 1441334Notes

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]=[C:25](\[F:37])/[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]([CH3:34])[CH3:35])[C:31]([CH3:36])=[N:30][CH:29]=4)[C:25]([F:37])=[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) (0.36 g, 1.25 mmol) and (2Z)-3-(dimethylamino)-2-fluoro-1-(1-isopropyl-2-methyl-1H-imidazol-5-yl)prop-2-en-1-one (Method 14; 0.15 g, 0.63 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 (180 mg, 62%). NMR (400.132 MHz, CDCl3) 8.21 (d, 1H), 7.56 (d, 1H), 7.34 (d, 2H), 6.80 (s, 1H), 6.59 (m, 3H), 5.55 (septet, 1H), 3.62 (t, 1H), 3.21-3.15 (m, 1H), 2.74-2.68 (m, 1H), 2.58 (s, 3H), 2.28-2.22 (m, 2H), 2.05-1.98 (m, 1H), 1.96-1.86 (m, 1H), 1.45 (d, 6H), 0.79-0.72 (m, 2H), 0.44-0.37 (m, 2H); m/z 464.

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-e917914090c048e0b7f5e5165030cbfa
Source dataset: uspto-grants-2010_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07655652B2

Reaction notes

Loading…