Pyridine → N,N-Dimethyl-5-[3-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-5-[(4-methyl-1,3-thiazol-2-yl)carbamoyl]phenoxy]pyrazine-2-carboxamide

HRID 600528Notes

Reaction equation

HRID 600528 reaction equation
ClC(N(C)C)=C(C)C.[CH3:9][N:10]([CH3:37])[C:11]([C:13]1[N:14]=[CH:15][C:16]([O:19][C:20]2[CH:21]=[C:22]([CH:26]=[C:27]([O:29][C@H:30]3[CH2:34][CH2:33][N:32]([CH3:35])[C:31]3=[O:36])[CH:28]=2)[C:23]([OH:25])=O)=[N:17][CH:18]=1)=[O:12].[CH3:38][C:39]1[N:40]=[C:41]([NH2:44])[S:42][CH:43]=1.N1C=CC=CC=1>C(Cl)Cl>[CH3:37][N:10]([CH3:9])[C:11]([C:13]1[CH:18]=[N:17][C:16]([O:19][C:20]2[CH:21]=[C:22]([C:23](=[O:25])[NH:44][C:41]3[S:42][CH:43]=[C:39]([CH3:38])[N:40]=3)[CH:26]=[C:27]([O:29][C@H:30]3[CH2:34][CH2:33][N:32]([CH3:35])[C:31]3=[O:36])[CH:28]=2)=[CH:15][N:14]=1)=[O:12]

Participants

6

Reactant 4

HCID 1049PyridineHCID 741432-Amino-4-methylthiazoleHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 59761148HCID 59761148, compound2×

Product 1

HCID 24951579N,N-Dimethyl-5-[3-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-5-[(4-methyl-1,3-thiazol-2-yl)carbamoyl]phenoxy]pyrazine-2-carboxamideYield 45%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-Chloro-N,N,2-trimethyl-prop-1-en-1-amine (0.14 mL, 1.1 mmol) was added to a solution of 3-[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-benzoic acid (Intermediate 45) (358 mg, 0.9 mmol) in DCM (7 mL) and stirred at ambient temperature for 30 minutes. 4-Methyl-1,3-thiazol-2-amine (CAS no. 1603-91-4) (206 mg, 1.8 mmol) and pyridine (0.15 mL, 1.8 mmol) were added and the reaction stirred for 20 hours. The solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate (30 mL), washed with water (2×10 mL) and brine (10 mL), dried (MgSO4) and evaporated. The residue was purified by flash chromatography on silica eluting with a gradient of 0 to 5% methanol in DCM to afford the product (200 mg, 45%). 1H NMR δ (300 MHz, CDCl3) 2.09-2.22 (m, 1H), 2.25 (s, 3H), 2.50-2.65 (m, 1H), 2.93 (s, 3H), 3.18 (d, 6H), 3.34-3.55 (m, 2H), 4.86 (t, 1H), 6.56 (s, 1H), 7.16 (s, 1H), 7.37 (s, 1H), 7.54 (s, 1H), 8.37 (s, 1H), 8.51 (s, 1H), 10.0-11.0 (br s, 1H); m/z 497 (M+H+).

Workup

  1. stirringthe reaction stirred for 20 hours
  2. customThe solvent was removed under reduced pressure
  3. dissolutionThe residue was dissolved in ethyl acetate (30 mL)
  4. washwashed with water (2×10 mL) and brine (10 mL)
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customThe residue was purified by flash chromatography on silica eluting with a gradient of 0 to 5% methanol in DCM

Sources & evidence

ORD record
ord-24428df036bc48f1b7df6fb1ed858bb5
Source dataset
uspto-grants-2011_03
Patent number
US07902200B2

Reaction notes

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