Trifluoroacetic acid → HCID 66832598, compound

HRID 2044076Notes

Reaction equation

HRID 2044076 reaction equation
[C:1]([C:4]1[C:5]([NH:28][C:29]2[CH:34]=[CH:33][C:32]([C:35]([N:37]3[CH2:42][CH2:41][O:40][CH2:39][CH2:38]3)=[O:36])=[CH:31][CH:30]=2)=[CH:6][C:7]([N:14]2[CH2:19][CH2:18][CH2:17][C@@H:16]([NH:20]C(=O)OC(C)(C)C)[CH2:15]2)=[N:8][C:9]=1[O:10][CH2:11][CH2:12][CH3:13])(=[O:3])[NH2:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:20][C@@H:16]1[CH2:17][CH2:18][CH2:19][N:14]([C:7]2[CH:6]=[C:5]([NH:28][C:29]3[CH:34]=[CH:33][C:32]([C:35]([N:37]4[CH2:38][CH2:39][O:40][CH2:41][CH2:42]4)=[O:36])=[CH:31][CH:30]=3)[C:4]([C:1]([NH2:2])=[O:3])=[C:9]([O:10][CH2:11][CH2:12][CH3:13])[N:8]=2)[CH2:15]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66832997HCID 66832997, compound

Product 1

HCID 66832598HCID 66832598, compoundYield 86.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (R)-tert-butyl 1-(5-carbamoyl-4-(4-(morpholine-4-carbonyl)phenylamino)-6-propoxypyridin-2-yl)piperidin-3-ylcarbamate (530 mg, 0.910 mmol) in CH2Cl2 (5 mL) was treated with TFA (5 mL, 64.9 mmol) and stirred at rt for 1 hr. Solvent was removed by evaporation on a rotary evaporator. The residue was dissolved in CH2Cl2 and washed with NaHCO3 and concentrated to give 380 mg of (R)-6-(3-aminopiperidin-1-yl)-4-(4-(morpholine-4-carbonyl)phenylamino)-2-propoxynicotinamide as a white solid. LCMS: (M+H)+=483.36. 1H NMR (400 MHz, CDCl3) δ ppm 11.60 (1H, s), 7.94 (1H, br. s.), 7.41 (2H, d, J=8.35 Hz), 7.27 (2H, d, J=8.35 Hz), 6.03 (1H, s), 5.69 (1H, br. s.), 4.36 (2H, t, J=6.48 Hz), 4.06 (1 H, d, J=10.77 Hz), 3.86 (1H, d, J=12.96 Hz), 3.71 (8H, br. s.), 2.81-2.97 (2H, m), 2.75 (1H, dd, J=12.30, 9.23 Hz), 1.89-2.05 (1H, m), 1.80-1.88 (2H, m), 1.70-1.80 (1H, m), 1.53 (1H, ddd, J=10.44, 3.41, 3.30 Hz), 1.25-1.38 (1H, m), 1.05 (3H, t, J=7.36 Hz).

Workup

  1. customSolvent was removed by evaporation on a rotary evaporator
  2. dissolutionThe residue was dissolved in CH2Cl2
  3. washwashed with NaHCO3
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-0c734772ad6d4da98833cd9f0da4a273
Source dataset
uspto-grants-2013_11
Patent number
US08586751B2

Reaction notes

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