Trifluoroacetic acid → HCID 68051772, compound

HRID 2044070Notes

Reaction equation

HRID 2044070 reaction equation
C(OC([NH:8][C@@H:9]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[N:20]=[C:19]([NH:21][C:22]3[CH:27]=[CH:26][C:25]([N:28]4[CH2:33][CH2:32][N:31]([C:34]([O:36][CH2:37][C:38]5[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=5)=[O:35])[CH2:30][CH2:29]4)=[CH:24][CH:23]=3)[C:18]([C:44](=[O:46])[NH2:45])=[CH:17][CH:16]=2)[CH2:10]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:8][C@@H:9]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[N:20]=[C:19]([NH:21][C:22]3[CH:23]=[CH:24][C:25]([N:28]4[CH2:33][CH2:32][N:31]([C:34]([O:36][CH2:37][C:38]5[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=5)=[O:35])[CH2:30][CH2:29]4)=[CH:26][CH:27]=3)[C:18]([C:44](=[O:46])[NH2:45])=[CH:17][CH:16]=2)[CH2:10]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68065850HCID 68065850, compound

Product 1

HCID 68051772HCID 68051772, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of ((R)-benzyl 4-(4-(6-(3-(tert-butoxycarbonylamino)piperidin-1-yl)-3-carbamoylpyridin-2-ylamino)phenyl)piperazine-1-carboxylate) (4.71 g, 7.5 mmol) in CH2Cl2 (5 ml) was treated with 5 mL of TFA and stirred at rt for 5 h. The reaction mixture was concentrated and the residue was partitioned between 1N NaOH and CH2Cl2. The aqueous phase was extracted with CH2Cl2 and the combined organic layers were concentrated. The brown residue was purified by MPLC (ISCO, 8% NH4OH/MeOH/CH2Cl2, 120 g silica gel column) and the fractions containing product were combined and concentrated. The resulting solid was triturated with CH2Cl2 to obtain 1.9 g of (R)-benzyl 4-(4-(6-(3-aminopiperidin-1-yl)-3-carbamoylpyridin-2-ylamino) phenyl)piperazine-1-carboxylate as a white solid. A second trituration gave an additional 320 mg of product as a light yellow solid.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe residue was partitioned between 1N NaOH and CH2Cl2
  3. extractionThe aqueous phase was extracted with CH2Cl2
  4. concentrationthe combined organic layers were concentrated
  5. customThe brown residue was purified by MPLC (ISCO, 8% NH4OH/MeOH/CH2Cl2, 120 g silica gel column)
  6. additionthe fractions containing product
  7. concentrationconcentrated
  8. customThe resulting solid was triturated with CH2Cl2

Sources & evidence

ORD record
ord-2970993f78d84251af5f4302a3aa2a1f
Source dataset
uspto-grants-2013_11
Patent number
US08586751B2

Reaction notes

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