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

HRID 929114Notes

Reaction equation

HRID 929114 reaction equation
Cl[C:2]1[C:7]([CH:8]=O)=[C:6](Cl)[N:5]=[CH:4][N:3]=1.[NH2:11][CH2:12][C@@H:13]([OH:24])[CH2:14][O:15][C:16]1[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][C:17]=1[CH3:23].CCN(CC)CC.[NH2:32][C:33]1[CH:34]=[C:35]2[C:39](=[CH:40][C:41]=1[NH2:42])[C:38](=[O:43])[N:37]([CH:44]1[CH2:49][CH2:48][N:47]([CH3:50])[CH2:46][CH2:45]1)[C:36]2=[O:51].Cl.CC(N(C)C)=[O:55]>C(Cl)(Cl)Cl>[CH3:23][C:17]1[CH:18]=[C:19]([CH3:22])[CH:20]=[CH:21][C:16]=1[O:15][CH2:14][C@H:13]([OH:24])[CH2:12][NH:11][C:6]1[N:5]=[CH:4][NH:3][C:2](=[O:55])[C:7]=1[C:8]1[NH:32][C:33]2[C:41]([N:42]=1)=[CH:40][C:39]1[C:38](=[O:43])[N:37]([CH:44]3[CH2:45][CH2:46][N:47]([CH3:50])[CH2:48][CH2:49]3)[C:36](=[O:51])[C:35]=1[CH:34]=2

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 31374DimethylacetamideHCID 8196914,6-Dichloro-5-pyrimidinecarbaldehydeHCID 2133977(2R)-1-amino-3-(2,4-dimethylphenoxy)propan-2-olHCID 597616575,6-Diamino-2-(1-methyl-piperidin-4-yl)-isoindole-1,3-dione

Product 1

HCID 1362001702-{4-[(R)-3-(2,4-Dimethyl-phenoxy)-2-hydroxy-propylamino]-6-oxo-1,6-dihydro-pyrimidin-5-yl}-6-(1-methyl-piperidin-4-yl)-1H-1,3,6-triaza-s-indacene-5,7-dioneYield 17%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of 4,6-dichloro-pyrimidine-5-carbaldehyde (177 mg, 1.0 mmol) and (R)-1-amino-3-(2,4-dimethyl-phenoxy)-propan-2-ol (195.3 mg, 1.0 mmol) in chloroform (8 mL) was added Et3N (348 μL, 2.5 mmol). After it was stirred at the room temperature for 8 h, the reaction mixture was evaporated under reduced pressure thoroughly. The remaining residue was mixed with 5,6-diamino-2-(1-methyl-piperidin-4-yl)-isoindole-1,3-dione (274 mg, 1.0 mmol) in DMA (10 mL). After it was heated at 110° C. for 14 h, the reaction mixture was cooled to the room temperature and mixed with aqueous HCl solution (12 N, 1 mL). The resulting mixture was heated in a sealed vial at 110° C. for 3 h and evaporated to dryness. The residue was basified with NH3 in EtOH (2 M) and concentrated. Chromatography of the crude afforded the title compound (93 mg, 17% yield for 3 steps). 1H NMR (DMSO-d6) δ 1.62 (m, 2H), 1.97 (m, 2H), 2.14 (s, 3H, CH3), 2.17 (s, 3H, CH3), 2.17 (s, 3H, CH3), 2.38 (m, 2H), 2.89 (m, 2H), 3.80 (m, 1H), 3.90-4.02 (4H), 4.11 (m, 1H), 5.47 (br s, 1H, NH), 6.82 (d, J=6 Hz, 1H), 6.93 (d, J=6 Hz, 1H), 6.97 (s, 1H), 8.06 (s, 1H), 8.12 (s, 1H), 10.83 (br s, 1H, NH); ESI-MS m/z 572.3 (MH+).

Workup

  1. customthe reaction mixture was evaporated under reduced pressure thoroughly
  2. temperatureAfter it was heated at 110° C. for 14 h
  3. temperaturethe reaction mixture was cooled to the room temperature
  4. temperatureThe resulting mixture was heated in a sealed vial at 110° C. for 3 h
  5. customevaporated to dryness
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-03241f36bd10448b962718a4749c42ef
Source dataset
uspto-grants-2016_03
Patent number
US09290503B2

Reaction notes

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