Trifluoroacetic acid → (R)-6-(3-aminopiperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide

HRID 2044038Notes

Reaction equation

HRID 2044038 reaction equation
[C:1]([C:4]1[CH:5]=[CH:6][C:7]([N:25]2[CH2:30][CH2:29][CH2:28][C@@H:27]([NH:31]C(=O)OC(C)(C)C)[CH2:26]2)=[N:8][C:9]=1[NH:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)=[O:18])=[CH:13][CH:12]=1)(=[O:3])[NH2:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:31][C@@H:27]1[CH2:28][CH2:29][CH2:30][N:25]([C:7]2[CH:6]=[CH:5][C:4]([C:1]([NH2:2])=[O:3])=[C:9]([NH:10][C:11]3[CH:12]=[CH:13][C:14]([C:17]([N:19]4[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)=[O:18])=[CH:15][CH:16]=3)[N:8]=2)[CH2:26]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 49846385(R)-tert-butyl 1-(5-carbamoyl-6-(4-(morpholine-4-carbonyl)phenylamino)pyridin-2-yl)piperidin-3-ylcarbamate

Product 1

HCID 49846316(R)-6-(3-aminopiperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamideYield 99.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (R)-tert-butyl 1-(5-carbamoyl-6-(4-(morpholine-4-carbonyl)phenylamino)pyridin-2-yl)piperidin-3-ylcarbamate (1.7 g) in CH2Cl2 (3 ml) was treated with 3 ml of TFA and stirred at rt for 2 h. The reaction mixture was concentrated, basified with 1N NaOH, and extracted three times with CH2Cl2. The resulting organic layer was concentrated to obtained 1.367 g of (R)-6-(3-aminopiperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide as a pale yellow solid. LCMS: (M+H)+=425.08. 1H NMR (400 MHz, CDCl3) δ ppm 11.21 (1H, s), 7.71 (2H, d, J=8.56 Hz), 7.52 (1H, d, J=8.81 Hz), 7.38 (2H, d, J=8.56 Hz), 6.06 (1H, d, J=8.80 Hz), 5.62 (2H, s), 4.19 (1H, d, J=9.57 Hz), 4.06-4.14 (1H, m, J=13.35 Hz), 3.59-3.79 (8H, m), 3.03-3.13 (1H, m), 2.78-2.92 (2H, m), 1.95-2.06 (1H, m), 1.73-1.86 (1H, m), 1.51-1.64 (1H, m), 1.30-1.46 (1H, m).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. extractionextracted three times with CH2Cl2
  3. concentrationThe resulting organic layer was concentrated

Sources & evidence

ORD record
ord-ba9b1936c956490487ae98fde7c347a4
Source dataset
uspto-grants-2013_11
Patent number
US08586751B2

Reaction notes

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