2-{4-[(R)-3-(2,4-Dimethyl-phenoxy)-2-hydroxy-propylamino]-2-oxo-1,2-dihydro-pyridin-3-yl}-6-(1-methyl-piperidin-4-yl)-1H-1,3,6-triaza-s-indacene-5,7-dione → 2-{4-[(R)-3-(2,4-Dimethyl-phenoxy)-2-hydroxy-propylamino]-2-oxo-1,2-dihydro-pyridin-3-yl}-6-(1-methyl-piperidin-4-yl)-6,7-dihydro-3H-1,3,6-triaza-s-indacen-5-one

HRID 561923Notes

Reaction equation

HRID 561923 reaction equation
[CH3:1][C:2]1[CH:41]=[C:40]([CH3:42])[CH:39]=[CH:38][C:3]=1[O:4][CH2:5][C@H:6]([OH:37])[CH2:7][NH:8][C:9]1[CH:14]=[CH:13][NH:12][C:11](=[O:15])[C:10]=1[C:16]1[NH:17][C:18]2[C:26]([N:27]=1)=[CH:25][C:24]1[C:23](=O)[N:22]([CH:29]3[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]3)[C:21](=[O:36])[C:20]=1[CH:19]=2>CC(O)=O.[Zn]>[CH3:1][C:2]1[CH:41]=[C:40]([CH3:42])[CH:39]=[CH:38][C:3]=1[O:4][CH2:5][C@H:6]([OH:37])[CH2:7][NH:8][C:9]1[CH:14]=[CH:13][NH:12][C:11](=[O:15])[C:10]=1[C:16]1[NH:17][C:18]2[C:26](=[CH:25][C:24]3[CH2:23][N:22]([CH:29]4[CH2:30][CH2:31][N:32]([CH3:35])[CH2:33][CH2:34]4)[C:21](=[O:36])[C:20]=3[CH:19]=2)[N:27]=1

Participants

4

Reactant 1

HCID 1362002662-{4-[(R)-3-(2,4-Dimethyl-phenoxy)-2-hydroxy-propylamino]-2-oxo-1,2-dihydro-pyridin-3-yl}-6-(1-methyl-piperidin-4-yl)-1H-1,3,6-triaza-s-indacene-5,7-dione

Product 1

HCID 1784268622-{4-[(R)-3-(2,4-Dimethyl-phenoxy)-2-hydroxy-propylamino]-2-oxo-1,2-dihydro-pyridin-3-yl}-6-(1-methyl-piperidin-4-yl)-6,7-dihydro-3H-1,3,6-triaza-s-indacen-5-oneYield 84%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
90 °C

Procedure

2-{4-[(R)-3-(2,4-Dimethyl-phenoxy)-2-hydroxy-propylamino]-2-oxo-1,2-dihydro-pyridin-3-yl}-6-(1-methyl-piperidin-4-yl)-1H-1,3,6-triaza-s-indacene-5,7-dione (3.0 g, 5.26 mmol) was mixed with zinc dust (6.88 g, 10.52 mmol) in AcOH (150 mL). After it was heated at 90° C. for 2 h, the reaction mixture was filtered and the filtrate was evaporated at 95° C. (the bath temperature) under reduced pressure to dryness. The residue was basified with 28% aqueous NH4OH solution and concentrated. Chromatography of the residual crude with CH2Cl2/MeOH/28% aqueous NH4OH (90:10:1) afforded the title compound (2.45 g, 84%). 1H NMR (DMSO-d6) δ 1.70 (m, 2H), 1.80 (m, 2H), 2.05 (m, 2H), 2.20 (s, 3H, CH3), 2.22 (s, 3H, CH3), 2.28 (s, 3H, CH3), 2.89 (m, 2H), 3.57 (m, 1H), 3.79 (m, 1H), 3.95-4.09 (3H), 4.11 (m, 1H), 4.40 (s, 1H), 4.45 (s, 1H), 5.47 (d, J=3 Hz, 0.5H, NH), 5.54 (d, J=3 Hz, 0.5H, NH), 6.21 (m, 1H), 6.80-7.00 (3H), 7.30-7.39 (1.5H), 7.69 (s, 0.5H), 7.79 (s, 0.5H), 7.93 (s, 0.5H), 11.12 (br d, J=6 Hz, 1H, NH), 11.22 (br d, J=6 Hz, 1H, NH); ESI-MS m/z 557.7 (MH+).

Workup

  1. filtrationthe reaction mixture was filtered
  2. customthe filtrate was evaporated at 95° C. (the bath temperature) under reduced pressure to dryness
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-3df5a7b05e7e4623aba27dbe7073f7dd
Source dataset
uspto-grants-2011_11
Patent number
US08063225B2

Reaction notes

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