(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 methylamide

HRID 1441341Notes

Reaction equation

HRID 1441341 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]=[C:23](\[F:35])/[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]([CH3:32])[CH3:33])[C:29]([CH3:34])=[N:28][CH:27]=3)[C:23]([F:35])=[CH:22][N:18]=2)=[CH:12][CH:11]=1)=[O:4]

Participants

4

Reactant 2

HCID 58127046(2Z)-3-(dimethylamino)-2-fluoro-1-(1-isopropyl-2-methyl-1H-imidazol-5-yl)prop-2-en-1-oneHCID 178485743(R)-1-(4-Guanidino-phenyl)-pyrrolidine-2-carboxylic acid methylamide

Product 1

HCID 68686045(R)-1-{4-[5-Fluoro-4-(3-isopropyl-2-methyl-3H-imidazol-4-yl)-pyrimidin-2-ylamino]-phenyl}-pyrrolidine-2-carboxylic acid methylamideYield 40%

Reagents, catalysts & solvents 1

HCID 80192-MethoxyethanolSolvent

Conditions

Temperature
200 °C

Procedure

(R)-1-(4-Guanidino-phenyl)-pyrrolidine-2-carboxylic acid methylamide (Method 59; 0.22 g, 0.82 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. Solvent was removed in vacuo and chromatographed. The product was passed purified by HPLC, and the required fractions were combined and basified with K2CO3 (0.5 g), extracted with DCM (2×50 ml), dried and solvent removed in vacuo to yield a yellow solid (110 mg, 40%). NMR (400.132 MHz, CDCl3) 8.21 (d, 1H), 7.56 (d, 1H), 7.34 (d, 2H), 6.79 (s, 1H), 6.60 (d, 2H), 6.56 (s, 1H), 5.56 (septet, 1H), 3.99 (t, 1H), 3.64 (t, 1H), 3.20 (q, 1H), 2.80 (d, 3H), 2.58 (s, 3H), 2.29-2.24 (m, 2H), 2.06-1.89 (m, 2H), 1.45 (d, 6H); m/z 438.

Workup

  1. customSolvent was removed in vacuo
  2. customchromatographed
  3. customThe product was passed purified by HPLC
  4. extractionextracted with DCM (2×50 ml)
  5. customdried
  6. customsolvent removed in vacuo

Sources & evidence

ORD record
ord-b402279218594b28b02986bd5f4521d6
Source dataset
uspto-grants-2010_02
Patent number
US07655652B2

Reaction notes

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