Triethylamine → HCID 58826320, compound

HRID 447239Notes

Reaction equation

HRID 447239 reaction equation
Cl.[NH2:2][C@H:3]([CH2:8][C:9]1[CH:10]=[C:11]2[C:15](=[C:16]([CH3:18])[CH:17]=1)[NH:14][N:13]=[CH:12]2)[C:4]([O:6][CH3:7])=[O:5].C1C(=O)N(OC(ON2C(=O)CCC2=O)=O)[C:21](=[O:22])C1.C(N(CC)CC)C.[NH:44]1[CH2:49][CH2:48][CH:47]([C:50]2[C:51](=[O:60])[NH:52][C:53]3[C:58]([CH:59]=2)=[CH:57][CH:56]=[CH:55][CH:54]=3)[CH2:46][CH2:45]1>CN(C)C=O>[CH3:18][C:16]1[CH:17]=[C:9]([CH2:8][C@@H:3]([NH:2][C:21]([N:44]2[CH2:45][CH2:46][CH:47]([C:50]3[C:51](=[O:60])[NH:52][C:53]4[C:58]([CH:59]=3)=[CH:57][CH:56]=[CH:55][CH:54]=4)[CH2:48][CH2:49]2)=[O:22])[C:4]([O:6][CH3:7])=[O:5])[CH:10]=[C:11]2[C:15]=1[NH:14][N:13]=[CH:12]2

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 676246Di(succinimido) carbonateHCID 183210463-(Piperidin-4-yl)quinolin-2(1H)-oneHCID 66603772HCID 66603772, compound

Product 1

HCID 58826320HCID 58826320, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (R)-methyl 2-amino-3-(7-methyl-1H-indazol-5-yl)propanoate hydrochloride (7.26 g, 27.0 mmoles) in dimethylformamide (50 mL) at room temperature was added N,N′-disuccinimidyl carbonate (7.60 g, 29.7 mmoles) followed by triethylamine (11.29 mL, 81 mmoles). The resulting mixture was stirred for 30 min and treated with 3-(piperidin-4-yl)quinolin-2(1H)-one (6.77 g, 29.9 mmoles) in portions. The reaction was allowed to stir for 24 h. The mixture was concentrated, dissolved in ethyl acetate, and washed sequentially with water, brine, and 0.5 N HCl (2×). The organic phase was dried over magnesium sulfate, filtered, and concentrated. The resulting residue was purified by flash chromatography (silica gel, 20:1 ethyl acetate/methanol) to give 11.9 g (78%). 1H-NMR (CD3OD) δ 13.0 (s, 1H), 11.8 (s, 1H), 7.98 (s, 1H), 7.63 (d, J=7.6 Hz, 1H), 7.57 (s, 1H), 7.45-7.41 (m, 2H), 7.27 (d, J=8.2Hz, 1H), 7.16 (t, J=7.9 Hz, 1H), 7.03 (s, 1H), 6.85 (d, J=7.9 Hz, 1H), 4.31-4.26 (m, 1H), 4.10-4.08 (m, 2H), 3.60 (s, 3H), 3.07-3.01 (m, 2H), 2.93-2.88 (m, 1H), 2.77-2.67 (m, 2H), 2.48 (s, 3H), 1.78-1.72 (m, 2H), 1.34-1.26 (m, 2H). Mass spec.: 488.52 (MH)+.

Workup

  1. stirringto stir for 24 h
  2. concentrationThe mixture was concentrated
  3. dissolutiondissolved in ethyl acetate
  4. washwashed sequentially with water, brine, and 0.5 N HCl (2×)
  5. dry with materialThe organic phase was dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was purified by flash chromatography (silica gel, 20:1 ethyl acetate/methanol)
  9. customto give 11.9 g (78%)

Sources & evidence

ORD record
ord-b1b42779170241f590b2defd7e0cc020
Source dataset
uspto-grants-2013_07
Patent number
US08481546B2

Reaction notes

Loading…