(2Z)-3-(dimethylamino)-2-fluoro-1-(1-isopropyl-2-methyl-1H-imidazol-5-yl)prop-2-en-1-one → (2S)-1-(4-(5-fluoro-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidin-2-ylamino)phenyl)-N,N-dimethylpyrrolidine-2-carboxamide

HRID 1441340Notes

Reaction equation

HRID 1441340 reaction equation
[CH3:1][N:2]([CH3:20])[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:23]=[C:24](\[F:36])/[C:25]([C:27]1[N:31]([CH:32]([CH3:34])[CH3:33])[C:30]([CH3:35])=[N:29][CH:28]=1)=O>C(O)CCC>[CH3:1][N:2]([CH3:20])[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:25]([C:27]3[N:31]([CH:32]([CH3:33])[CH3:34])[C:30]([CH3:35])=[N:29][CH:28]=3)[C:24]([F:36])=[CH:23][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 178484576HCID 178484576, compound

Product 1

HCID 44578694(2S)-1-(4-(5-fluoro-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidin-2-ylamino)phenyl)-N,N-dimethylpyrrolidine-2-carboxamideYield 31%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
200 °C

Procedure

(S)-1-(4-Guanidino-phenyl)-pyrrolidine-2-carboxylic acid dimethylamide (Method 54; 0.5 g, 1.82 mmol) and (2Z)-3-(dimethylamino)-2-fluoro-1-(1-isopropyl-2-methyl-1H-imidazol-5-yl)prop-2-en-1-one (Method 14; 0.2 g, 0.83 mmol) were heated at reflux in butanol (7 ml) overnight. LCMS indicated only 7% product. The reaction was transferred to a microwave tube and heated at 200° C. for 2 hours. LCMS indicated 15% starting material and mainly product. The solvent was removed in vacuo and chromatographed. The product was purified by HPLC and the required fractions were combined and basified with K2CO3 (0.5 g), extracted with DCM (2×50 ml), dried and the solvent removed in vacuo to yield a yellow solid (101 mg, 31%). NMR (400.132 MHz, CDCl3) 8.18 (d, 1H), 7.56 (d, 1H), 7.24 (d, 2H), 6.69 (s, 1H), 6.42 (d, 2H), 5.59 (septet, 1H), 4.51 (dd, 1H), 3.64 (dt, 1H), 3.41 (q, 1H), 3.16 (s, 3H), 2.98 (s, 3H), 2.56 (s, 3H), 2.38-2.28 (m, 1H), 2.25-2.14 (m, 1H), 2.08-1.98 (m, 2H), 1.39 (t, 6H); m/z 452.

Workup

  1. customThe reaction was transferred to a microwave tube
  2. customThe solvent was removed in vacuo
  3. customchromatographed
  4. customThe product was purified by HPLC
  5. extractionextracted with DCM (2×50 ml)
  6. customdried
  7. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-0596e12ff2aa451ab90d55a0b5293cad
Source dataset
uspto-grants-2010_02
Patent number
US07655652B2

Reaction notes

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