Diisopropylethylamine → HCID 89726475, compound

HRID 1777728Notes

Reaction equation

HRID 1777728 reaction equation
Br[C:2]1[S:6][CH:5]=[N:4][C:3]=1[C:7]([O:9][CH3:10])=[O:8].[C:11]([N:18]1[CH2:23][CH2:22][NH:21][CH2:20][C@H:19]1[CH3:24])([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12].CCN(C(C)C)C(C)C>CN1C(=O)CCC1.CC(=O)OCC>[C:14]([O:13][C:11]([N:18]1[CH2:23][CH2:22][N:21]([C:2]2[S:6][CH:5]=[N:4][C:3]=2[C:7]([O:9][CH3:10])=[O:8])[CH2:20][C@H:19]1[CH3:24])=[O:12])([CH3:17])([CH3:15])[CH3:16]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 10262201tert-Butyl (2R)-2-methylpiperazine-1-carboxylateHCID 40787018Methyl 5-bromo-1,3-thiazole-4-carboxylate

Product 1

HCID 89726475HCID 89726475, compoundYield 30.8%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of methyl 5-bromo-1,3-thiazole-4-carboxylate (3 g) in NMP (30 mL) was added (R)-1-N-Boc-2-methylpiperazine (2.76 g) followed by DIPEA (10.1 mL). The resulting solution was stirred at 120° C. for 1.5 d, at RT over weekend and at 120° C. for 7 h. After cooling down, the reaction mixture was diluted with EA and washed with sat. aq. NaHCO3, 1M HCl and sat. aq NaCl. The aq. phases were extracted with EA. The combined org. layers were dried over Na2SO4, filtrated off and evaporated in vacuo. The crude was purified by CC (Biotage, SNAP 100 g cartridge, solvent A: Hept; solvent B: EA; gradient in % B: 0 for 10CV, 0 to 10 over 5CV, 10 for 5CV, 10 to 20 over 5CV, 20 for 5CV, 20 to 30 over 5CV, 30 for 5CV) to afford 1.42 g of yellow oil. LC-MS (B): tR=0.84 min; [M+H]+: 342.08.

Workup

  1. temperatureAfter cooling down
  2. washwashed with sat. aq. NaHCO3, 1M HCl and sat. aq NaCl
  3. extractionThe aq. phases were extracted with EA
  4. dry with materiallayers were dried over Na2SO4
  5. filtrationfiltrated off
  6. customevaporated in vacuo
  7. customThe crude was purified by CC (Biotage, SNAP 100 g cartridge, solvent A: Hept; solvent B: EA; gradient in % B: 0 for 10CV, 0 to 10 over 5CV, 10 for 5CV, 10 to 20 over 5CV, 20 for 5CV, 20 to 30 over 5CV, 30 for 5CV)

Sources & evidence

ORD record
ord-076e2cae0c914f1b89abd6e200a6f4b8
Source dataset
uspto-grants-2016_02
Patent number
US09266876B2

Reaction notes

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