(S)-1-tert-butyl 2-methyl 4-(6-amino-5-(4-(tert-butoxycarbonyl)-3-fluorophenyl)pyridin-3-yl)-1H-pyrrole-1,2(2H,5H)-dicarboxylate → (2S,4R)-1-tert-butyl 2-methyl 4-(6-amino-5-(4-(tert-butoxycarbonyl)-3-fluorophenyl)pyridin-3-yl)pyrrolidine-1,2-dicarboxylate

HRID 596106Notes

Reaction equation

HRID 596106 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH2:12][N:11]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@H:10]([C:20]([O:22][CH3:23])=[O:21])[CH:9]=2)=[CH:4][C:3]=1[C:24]1[CH:29]=[CH:28][C:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[C:26]([F:37])[CH:25]=1>CO.[Pd]>[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C@@H:8]2[CH2:12][N:11]([C:13]([O:15][C:16]([CH3:18])([CH3:17])[CH3:19])=[O:14])[C@H:10]([C:20]([O:22][CH3:23])=[O:21])[CH2:9]2)=[CH:4][C:3]=1[C:24]1[CH:29]=[CH:28][C:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[C:26]([F:37])[CH:25]=1

Participants

4

Reactant 1

HCID 118045728(S)-1-tert-butyl 2-methyl 4-(6-amino-5-(4-(tert-butoxycarbonyl)-3-fluorophenyl)pyridin-3-yl)-1H-pyrrole-1,2(2H,5H)-dicarboxylate

Product 1

HCID 118045509(2S,4R)-1-tert-butyl 2-methyl 4-(6-amino-5-(4-(tert-butoxycarbonyl)-3-fluorophenyl)pyridin-3-yl)pyrrolidine-1,2-dicarboxylateYield 64%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A degassed solution of (S)-1-tert-butyl 2-methyl 4-(6-amino-5-(4-(tert-butoxycarbonyl)-3-fluorophenyl)pyridin-3-yl)-1H-pyrrole-1,2(2H,5H)-dicarboxylate (470 mg, 0.915 mmol) in methanol (40 mL) was treated with 10 wt. % Pd/C (3.214 g, 3.02 mmol). The system was degassed again, then charged with 1 atm hydrogen overnight. At completion, the reaction degassed, then treated ammonia gas then filtered over Celite. The cake was reslurried in methanol, treated with ammonia gas, and filtered to retrieve additional product. The process was repeated until no further product eluted from filter cake. The combined organics were concentrated to provide (2S,4R)-1-tert-butyl 2-methyl 4-(6-amino-5-(4-(tert-butoxycarbonyl)-3-fluorophenyl)pyridin-3-yl)pyrrolidine-1,2-dicarboxylate (300 mg, 64%). LCMS (m/z): 516.1 (MH+), 0.89 min.

Workup

  1. customThe system was degassed again
  2. additioncharged with 1 atm hydrogen overnight
  3. customAt completion, the reaction degassed
  4. filtrationtreated ammonia gas then filtered over Celite
  5. additiontreated with ammonia gas
  6. filtrationfiltered
  7. washeluted
  8. filtrationfrom filter cake
  9. concentrationThe combined organics were concentrated

Sources & evidence

ORD record
ord-eeb59863ec6441d19173b892636313c0
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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