tert-Butyl piperazine-1-carboxylate → HCID 68817460, compound

HRID 2105220Notes

Reaction equation

HRID 2105220 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:12][CH2:11][CH2:10][CH:9]2[C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=3)[CH:14]=2)[N:5]=[C:4]([NH:24][C:25]2[CH:29]=[C:28]([CH3:30])[NH:27][N:26]=2)[CH:3]=1.[C:31]([O:35][C:36]([N:38]1[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1)=[O:37])([CH3:34])([CH3:33])[CH3:32]>O1CCOCC1>[C:31]([O:35][C:36]([N:38]1[CH2:43][CH2:42][N:41]([C:2]2[N:7]=[C:6]([N:8]3[CH2:12][CH2:11][CH2:10][CH:9]3[C:13]3[O:17][N:16]=[C:15]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=4)[CH:14]=3)[N:5]=[C:4]([NH:24][C:25]3[CH:29]=[C:28]([CH3:30])[NH:27][N:26]=3)[CH:3]=2)[CH2:40][CH2:39]1)=[O:37])([CH3:34])([CH3:32])[CH3:33]

Participants

4

Reactant 2

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 11281654HCID 11281654, compound

Product 1

HCID 68817460HCID 68817460, compoundYield 25%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of 6-chloro-4-(5-methyl-1H-pyrazol-3-ylamino)-2-[2-{3-(pyrid-2-yl)isoxazol-5-yl}pyrrolidin-1-yl]pyrimidine (Example 17) (250 mg, 0.6 mmol) and N-(tert-butoxycarbonyl)piperazine (222 mg, 6.0 mmol) in 1,4-dioxane (4 ml) was heated at 160° C. in a sealed vessel under microwave irradiation for 90 minutes. The crude reaction mixture was purified by reverse phase HPLC using a C18 column eluting with water/acetonitrile/TFA (95:5:0.2 decreasing in polarity to 0:100:0.2). Product containing fractions were combined and passed through an isolute SCX-2 ion exchange column. The column was eluted with methanol to elute any neutrals, followed by 7M methanolic ammonia to elute the product. The solvent was removed by evaporation to afford the desired product (85 mg, 25%) as a white solid.

Workup

  1. customThe crude reaction mixture
  2. customwas purified by reverse phase HPLC
  3. washeluting with water/acetonitrile/TFA (95:5:0.2 decreasing in polarity to 0:100:0.2)
  4. additionProduct containing fractions
  5. washThe column was eluted with methanol
  6. washto elute any neutrals
  7. washto elute the product
  8. customThe solvent was removed by evaporation

Sources & evidence

ORD record
ord-1e6f333c253d42cf8ee05ad74552d752
Source dataset
uspto-grants-2009_08
Patent number
US07579349B2

Reaction notes

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