Acetic Acid → HCID 178476386, compound

HRID 929129Notes

Reaction equation

HRID 929129 reaction equation
[CH3:1][C:2]1[CH:45]=[C:44]([CH3:46])[CH:43]=[CH:42][C:3]=1[O:4][CH2:5][C@H:6]([OH:41])[CH2:7][NH:8][C:9]1[CH:14]=[CH:13][NH:12][C:11](=[O:15])[C:10]=1[C:16]1[NH:27][C:26]2[C:18](=[CH:19][C:20]3[CH2:21][N:22]([CH:29]4[CH2:34][CH2:33][N:32]([CH2:35][CH2:36][S:37]([CH3:40])(=[O:39])=[O:38])[CH2:31][CH2:30]4)[C:23](=[O:28])[C:24]=3[CH:25]=2)[N:17]=1.[CH3:47][C:48](O)=[O:49]>>[CH3:1][C:2]1[CH:45]=[C:44]([CH3:46])[CH:43]=[CH:42][C:3]=1[O:4][CH2:5][CH:6]([O:41][C:48](=[O:49])[CH3:47])[CH2:7][NH:8][C:9]1[CH:14]=[CH:13][NH:12][C:11](=[O:15])[C:10]=1[C:16]1[NH:27][C:26]2[C:18]([N:17]=1)=[CH:19][C:20]1[CH2:21][N:22]([CH:29]3[CH2:34][CH2:33][N:32]([CH2:35][CH2:36][S:37]([CH3:40])(=[O:39])=[O:38])[CH2:31][CH2:30]3)[C:23](=[O:28])[C:24]=1[CH:25]=2

Participants

3

Reactant 2

HCID 176Acetic AcidHCID 178426864HCID 178426864, compound

Product 1

HCID 178476386HCID 178476386, compound

Procedure

A solution of 2-{4-[(R)-3-(2,4-Dimethyl-phenoxy)-2-hydroxy-propylamino]-2-oxo-1,2-dihydro-pyridin-3-yl}-6-[1-(2-methanesulfonyl-ethyl)-piperidin-4-yl]-6,7-dihydro-3H-1,3,6-triaza-s-indacen-5-one (65 mg, 0.1 mmol) in HOAc (20 mL) was refluxed for 32 h and was evaporated. The residue was diluted with a mixed solvent of DCM/MeOH (1:5), basified with 28% aqueous NH4OH solution and concentrated. Chromatography of the residual crude with CH2Cl2/MeOH/28% aqueous NH4OH (110:10:1) followed by HPLC re-purification afforded the title compound in TFA salt form (8.69 mg, 11%). 1H NMR (DMSO-d6) δ 1.99-2.12 (4H), 2.05 (s, 3H, CH3), 2.16 (s, 3H, CH3), 2.22 (s, 3H, CH3), 3.15 (s, 3H, CH3), 3.25 (m, 2H), 3.52 (m, 2H), 3.60-3.78 (5H), 3.90 (s, 1H), 4.10-4.38 (4H), 4.49 (br s, 2H), 5.43 (br s, 2H, NH), 6.28 (d, J=8 Hz, 1H), 6.84 (d, J=6 Hz, 1H), 6.94 (d, J=6 Hz, 1H), 6.99 (s, 1H), 7.40 (m, 1H), 7.80 (br s, 1H), 9.80 (br s, 1H), 11.14 (br s, NH), 11.33 (br d, J=6 Hz, 1H, NH); ESI-MS m/z 691.7 (MH+).

Workup

  1. customwas evaporated
  2. additionThe residue was diluted with a mixed solvent of DCM/MeOH (1:5)
  3. concentrationconcentrated
  4. customChromatography of the residual crude with CH2Cl2/MeOH/28% aqueous NH4OH (110:10:1) followed by HPLC re-purification

Sources & evidence

ORD record
ord-3a7ddf24187c40eda7380934e9b48a3a
Source dataset
uspto-grants-2016_03
Patent number
US09290503B2

Reaction notes

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