tert-Butyl piperazine-1-carboxylate → HCID 131736841, compound

HRID 1487263Notes

Reaction equation

HRID 1487263 reaction equation
[NH2:1][C:2]1[C:3]2[N:14]([CH2:15][O:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH:13]=[C:12]([CH2:24][CH2:25][CH2:26][CH:27]=O)[C:4]=2[N:5]=[C:6]([CH2:8][CH2:9][CH2:10][CH3:11])[N:7]=1.[N:29]1([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[NH2:1][C:2]1[C:3]2[N:14]([CH2:15][O:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH:13]=[C:12]([CH2:24][CH2:25][CH2:26][CH2:27][N:32]3[CH2:33][CH2:34][N:29]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:30][CH2:31]3)[C:4]=2[N:5]=[C:6]([CH2:8][CH2:9][CH2:10][CH3:11])[N:7]=1

Participants

5

Reactant 3

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 118453815HCID 118453815, compound

Product 1

HCID 131736841HCID 131736841, compoundYield 125.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A suspension of 4-(4-amino-5-((benzyloxy)methyl)-2-butyl-5H-pyrrolo[3,2-d]pyrimidin-7-yl)butanal (268 mg, 0.704 mmol) and 4 Å molecular sieves in anhydrous dichloromethane (20 mL) was placed under nitrogen and tert-butyl piperazine-1-carboxylate (262 mg, 1.409 mmol) added. The reaction mixture was stirred at ambient temperature for 1 min then sodium triacetoxyborohydride (299 mg, 1.409 mmol) added and the reaction stirred for a further 30 min, Additional 4 Å molecular sieves were added and the reaction mixture stirred at ambient temperature for an additional 16.5 hours, The reaction mixture was filtered through celite and the cake washed with DCM. The solvent was removed in vacuo to give a viscous yellow oil. The oil was redissolved in DCM (50 mL). The organic layer was washed with saturated sodium hydrogen carbonate solution (50 mL), the layers separated and the aqueous layer back-extracted with DCM (2×25 mL). The combined organic phases were dried through a hydrophobic frit and concentrated in vacuo to give a yellow gum (488 mg). The sample was dissolved in dichloromethane and purified by chromatography on a silica cartridge (100 g) using a 0-10% MeOH:TBME gradient over 40 mins. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a pale yellow gum (338 mg).

Workup

  1. stirringthe reaction stirred for a further 30 min
  2. additionAdditional 4 Å molecular sieves were added
  3. stirringthe reaction mixture stirred at ambient temperature for an additional 16.5 hours
  4. filtrationThe reaction mixture was filtered through celite
  5. washthe cake washed with DCM
  6. customThe solvent was removed in vacuo
  7. customto give a viscous yellow oil
  8. washThe organic layer was washed with saturated sodium hydrogen carbonate solution (50 mL)
  9. customthe layers separated
  10. extractionthe aqueous layer back-extracted with DCM (2×25 mL)
  11. customThe combined organic phases were dried through a hydrophobic frit
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-23b8531145464e36a91e3bc4a2567d97
Source dataset
uspto-grants-2016_08
Patent number
US09428512B2

Reaction notes

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