N,N-Dimethylglycine → (R)-6-(3-(2-(dimethylamino) acetamido)piperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide

HRID 2044042Notes

Reaction equation

HRID 2044042 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]2[CH:16]=[CH:15][C:11]([C:12]([NH2:14])=[O:13])=[C:10]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([C:24]([N:26]4[CH2:31][CH2:30][O:29][CH2:28][CH2:27]4)=[O:25])=[CH:20][CH:19]=3)[N:9]=2)[CH2:3]1.[CH3:32][N:33]([CH3:38])[CH2:34][C:35](O)=[O:36].C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(Cl)Cl>[CH3:32][N:33]([CH3:38])[CH2:34][C:35]([NH:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]2[CH:16]=[CH:15][C:11]([C:12]([NH2:14])=[O:13])=[C:10]([NH:17][C:18]3[CH:19]=[CH:20][C:21]([C:24]([N:26]4[CH2:31][CH2:30][O:29][CH2:28][CH2:27]4)=[O:25])=[CH:22][CH:23]=3)[N:9]=2)[CH2:3]1)=[O:36]

Participants

7

Reactant 4

HCID 673N,N-DimethylglycineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 49846316(R)-6-(3-aminopiperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide

Product 1

HCID 66833374(R)-6-(3-(2-(dimethylamino) acetamido)piperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamideYield 41.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of (R)-6-(3-aminopiperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide (40 mg, 0.094 mmol), 2-(dimethylamino)acetic acid (19.43 mg, 0.188 mmol), N,N-diisopropylethylamine (0.033 mL, 0.188 mmol), and HATU (71.7 mg, 0.188 mmol) in DMF was stirred at rt for 1 h. The reaction mixture was diluted with CH2Cl2, washed with satd NaHCO3, separated, and concentrated. The residue was purified (ISCO, 5% NH4OH/MeOH/CH2Cl2, 40 g silica gel column) to obtain 20 mg of (R)-6-(3-(2-(dimethylamino) acetamido)piperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide as a light yellow solid. LCMS: (M+H)+=510.40. 1H NMR (400 MHz, CDCl3) δ ppm 11.21 (1H, s), 7.69 (2H, d, J=8.56 Hz), 7.53 (1H, d, J=9.06 Hz), 7.37 (2H, d, J=8.56 Hz), 7.30 (1H, d, J=7.81 Hz), 6.12 (1H, d, J=8.81 Hz), 5.60 (1H, s), 3.96 (1H, dd, J=13.22, 3.15 Hz), 3.78-3.88 (1H, m), 3.60-3.78 (8H, m), 3.41-3.56 (2H, m), 2.92 (2H, s), 2.22 (6H, s), 1.65-2.03 (4H, m).

Workup

  1. washwashed with satd NaHCO3
  2. customseparated
  3. concentrationconcentrated
  4. customThe residue was purified (ISCO, 5% NH4OH/MeOH/CH2Cl2, 40 g silica gel column)

Sources & evidence

ORD record
ord-5f6954808b234435b3372c984e2de29c
Source dataset
uspto-grants-2013_11
Patent number
US08586751B2

Reaction notes

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