Triethylamine → 4-[6-(5-Methanesulfonyl-2,3-dihydro-indol-1-yl)-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid 1-tert-butoxycarbonyl-pyrrolidin-3-yl ester

HRID 448591Notes

Reaction equation

HRID 448591 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([OH:13])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[N+](C1C=CC([C:28](Cl)=[O:29])=CC=1)([O-])=O.[CH3:33][S:34]([C:37]1[CH:38]=[C:39]2[C:43](=[CH:44][CH:45]=1)[N:42]([C:46]1[CH:51]=[C:50]([O:52][CH:53]3[CH2:58][CH2:57][NH:56][CH2:55][CH2:54]3)[N:49]=[CH:48][N:47]=1)[CH2:41][CH2:40]2)(=[O:36])=[O:35]>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([O:13][C:28]([N:56]2[CH2:57][CH2:58][CH:53]([O:52][C:50]3[CH:51]=[C:46]([N:42]4[C:43]5[C:39](=[CH:38][C:37]([S:34]([CH3:33])(=[O:36])=[O:35])=[CH:45][CH:44]=5)[CH2:40][CH2:41]4)[N:47]=[CH:48][N:49]=3)[CH2:54][CH2:55]2)=[O:29])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 85024-Nitrobenzoyl chlorideHCID 44169391-Boc-3-pyrrolidinolHCID 667096685-(Methylsulfonyl)-1-(6-(piperidin-4-yloxy)pyrimidin-4-yl)indoline

Product 1

HCID 668943574-[6-(5-Methanesulfonyl-2,3-dihydro-indol-1-yl)-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid 1-tert-butoxycarbonyl-pyrrolidin-3-yl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent4×

Procedure

3-Hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester (0.37 g, 2 mmol) was dissolved in 4 mL of DCM with triethylamine (0.28 mL, 2 mmol). 4-Nitro-benzoyl chloride (0.4 g, 2 mmol) was added and the mixture was stirred at room temperature for 12 h. It was then diluted with DCM and washed with saturated NaHCO3 (3×20 mL). The organic layer was dried, filtered and evaporated. The residue was dissolved in DCM (4 mL) with triethylamine (0.36 mL, 2.6 mmol) and 4b (0.49 g, 1.3 mmol) was added. The mixture was stirred at room temperature for 8 h, diluted with DCM and washed with saturated NaHCO3. The organic layer was evaporated to afford 21a, LCMS 588.2 (MH+).

Workup

  1. washwashed with saturated NaHCO3 (3×20 mL)
  2. customThe organic layer was dried
  3. filtrationfiltered
  4. customevaporated
  5. additionwas added
  6. stirringThe mixture was stirred at room temperature for 8 h
  7. washwashed with saturated NaHCO3
  8. customThe organic layer was evaporated

Sources & evidence

ORD record
ord-c4979793de73432aadb09d46dbf5b998
Source dataset
uspto-grants-2013_07
Patent number
US08481731B2

Reaction notes

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