1,2-Dichloroethane → HCID 178463834, compound

HRID 2044054Notes

Reaction equation

HRID 2044054 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]([N:24]([CH2:27][CH3:28])[CH2:25][CH3:26])=[CH:20][CH:19]=3)[N:9]=2)[CH2:3]1.[C:29]([C:33]1[CH:37]=[C:36]([C:38](O)=[O:39])[NH:35][N:34]=1)([CH3:32])([CH3:31])[CH3:30].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(CC)CC>C1COCC1.C(Cl)Cl>[C:29]([C:33]1[CH:37]=[C:36]([C:38]([NH:1][C@@H:2]2[CH2:7][CH2:6][CH2:5][N:4]([C:8]3[CH:16]=[CH:15][C:11]([C:12]([NH2:14])=[O:13])=[C:10]([NH:17][C:18]4[CH:23]=[CH:22][C:21]([N:24]([CH2:27][CH3:28])[CH2:25][CH3:26])=[CH:20][CH:19]=4)[N:9]=3)[CH2:3]2)=[O:39])[NH:35][N:34]=1)([CH3:32])([CH3:30])[CH3:31]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 66832948(R)-6-(3-aminopiperidin-1-yl)-2-(4-(diethylamino)phenylamino)nicotinamideHCID 178441096HCID 178441096, compound

Product 1

HCID 178463834HCID 178463834, compoundYield 59%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of (R)-6-(3-aminopiperidin-1-yl)-2-(4-(diethylamino)phenylamino)nicotinamide (40 mg, 0.105 mmol), 3-tert-butyl-1H-pyrazole-5-carboxylic acid (21.11 mg, 0.125 mmol), EDC (30.1 mg, 0.157 mmol), HOBT (24.02 mg, 0.157 mmol), and Et3N (0.022 mL, 0.157 mmol) in THF (1 mL) was stirred at rt for 4 h. The reaction mixture was diluted with CH2Cl2, washed with satd. NaHCO3, and concentrated. The residue was purified by prep-HPLC. The product containing fractions were collected, basified with satd. Na2CO3, separated, and concentrated to give 33 mg of (R)-6-(3-(3-tert-butyl-1H-pyrazole-5-carboxamido) piperidin-1-yl)-2-(4-(diethylamino)phenylamino) nicotinamide as a yellow solid. LCMS: (M+H)+=533.30. 1H NMR (400 MHz, CDCl3) δ ppm 10.96 (1H, br. s.), 10.52 (1H, s), 7.44 (1H, d, J=8.79 Hz), 7.36 (2H, d, J=8.79 Hz), 7.06 (1 H, br. s.), 6.59 (2H, d, J=9.23 Hz), 6.00 (1H, d, J=8.79 Hz), 5.75 (1H, br. s.), 4.16-4.27 (1H, m), 3.82 (1H, br. s.), 3.58-3.72 (3H, m), 3.27 (4H, q, J=7.18 Hz), 1.86-1.96 (2H, m), 1.78 (1H, d, J=5.71 Hz), 1.62-1.70 (1H, m), 1.60 (2H, s), 1.33 (9H, s), 1.10 (6H, t, J=7.03 Hz).

Workup

  1. washwashed with satd
  2. concentrationNaHCO3, and concentrated
  3. customThe residue was purified by prep-HPLC
  4. additionThe product containing fractions
  5. customwere collected
  6. customNa2CO3, separated
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-63f7bf21030f4e41a60df03bab4380f7
Source dataset
uspto-grants-2013_11
Patent number
US08586751B2

Reaction notes

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