tert-Butyl 4-oxopiperidine-1-carboxylate → HCID 66755157, compound

HRID 1643978Notes

Reaction equation

HRID 1643978 reaction equation
[NH2:1][CH:2]1[CH2:6][CH2:5][N:4]([C:7](=[O:37])[CH:8]([N:15]2[C:19]3[CH:20]=[C:21]([Cl:24])[CH:22]=[CH:23][C:18]=3[N:17]([S:25]([C:28]3[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=3)(=[O:27])=[O:26])[C:16]2=[O:36])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:3]1.C(OC([N:45]1[CH2:50][CH2:49][C:48](=O)[CH2:47][CH2:46]1)=O)(C)(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C>C1COCC1>[Cl:24][C:21]1[CH:22]=[CH:23][C:18]2[N:17]([S:25]([C:28]3[CH:29]=[CH:30][C:31]([O:34][CH3:35])=[CH:32][CH:33]=3)(=[O:27])=[O:26])[C:16](=[O:36])[N:15]([CH:8]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[C:7](=[O:37])[N:4]3[CH2:5][CH2:6][CH:2]([NH:1][CH:48]4[CH2:49][CH2:50][NH:45][CH2:46][CH2:47]4)[CH2:3]3)[C:19]=2[CH:20]=1

Participants

5

Reactant 3

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 2724942TriacetoxyborohydrideHCID 66755125HCID 66755125, compound

Product 1

HCID 66755157HCID 66755157, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 88.0 mg (0.16 mmol) of 3-[2-(3-aminopyrrolidin-1-yl)-2-oxo-1-phenylethyl]-5-chloro-1-(4-methoxybenzenesulfonyl)-1,3-dihydrobenzimidazol-2-one (example 166) in 5 ml of THF was mixed with 34.0 mg (0.17 mmol) of 1-tert-butoxycarbonyl-4-piperidone and 162 mg of MP-triacetoxyborohydride resin (Argonaut, 2.55 mmol/g, 0.41 mmol) and shaken at room temperature overnight. The solid phase reagent was filtered off and washed with dichloromethane. The filtrate was concentrated in vacuo, and the residue was dissolved in 3 ml of dichloromethane, mixed with 3 ml of trifluoroacetic acid and stirred at room temperature for 2 h. The solvent and excess trifluoroacetic acid were removed in vacuo, and the residue was taken up again in toluene and concentrated in vacuo. The residue was dissolved in dichloromethane, mixed with 3 eq. of MP-carbonate (Argonaut, 1.69 mmol/g) and stirred at room temperature for 2 h. The solid phase reagent was filtered off and washed with dichloromethane. The filtrate was concentrated under reduced pressure and dried in vacuo. The residue was purified by preparative RP-HPLC (mobile phase: gradient from 10% to 80% acetonitrile in water, 0.1% trifluoroacetic acid as modulator). Yield: 73.0 mg (72%) of colorless solid

Workup

  1. filtrationThe solid phase reagent was filtered off
  2. washwashed with dichloromethane
  3. concentrationThe filtrate was concentrated in vacuo
  4. dissolutionthe residue was dissolved in 3 ml of dichloromethane
  5. additionmixed with 3 ml of trifluoroacetic acid
  6. stirringstirred at room temperature for 2 h
  7. customThe solvent and excess trifluoroacetic acid were removed in vacuo
  8. concentrationconcentrated in vacuo
  9. dissolutionThe residue was dissolved in dichloromethane
  10. additionmixed with 3 eq. of MP-carbonate (Argonaut, 1.69 mmol/g)
  11. stirringstirred at room temperature for 2 h
  12. filtrationThe solid phase reagent was filtered off
  13. washwashed with dichloromethane
  14. concentrationThe filtrate was concentrated under reduced pressure
  15. customdried in vacuo
  16. customThe residue was purified by preparative RP-HPLC (mobile phase: gradient from 10% to 80% acetonitrile in water, 0.1% trifluoroacetic acid as modulator)

Sources & evidence

ORD record
ord-4f74b27499614a87a318f935beeb464a
Source dataset
uspto-grants-2012_02
Patent number
US08119676B2

Reaction notes

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