Ethylorthoformate → HCID 86705762, compound

HRID 1054555Notes

Reaction equation

HRID 1054555 reaction equation
[NH2:1][C:2]1[C:3]([NH:9][C@H:10]2[C@@H:14]3[O:15][C:16]([CH3:19])([CH3:18])[O:17][C@@H:13]3[C@@H:12]([CH2:20][N:21]([CH3:36])[CH2:22][CH2:23][CH2:24][N:25]3[C:33](=[O:34])[C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[C:26]3=[O:35])[CH2:11]2)=[N:4][CH:5]=[N:6][C:7]=1[Cl:8].[CH:37]([O-])([O-])OCC>C(O)(=O)C>[Cl:8][C:7]1[N:6]=[CH:5][N:4]=[C:3]2[C:2]=1[N:1]=[CH:37][N:9]2[C@H:10]1[C@@H:14]2[O:15][C:16]([CH3:18])([CH3:19])[O:17][C@@H:13]2[C@@H:12]([CH2:20][N:21]([CH3:36])[CH2:22][CH2:23][CH2:24][N:25]2[C:26](=[O:35])[C:27]3[C:32](=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:33]2=[O:34])[CH2:11]1

Participants

4

Reactant 2

HCID 53630039EthylorthoformateHCID 86705763HCID 86705763, compound

Product 1

HCID 86705762HCID 86705762, compoundYield 92.8%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidCatalyst

Procedure

A solution of 2-(3-((((3aR,4R,6R,6aS)-6-((5-amino-6-chloropyrimidin-4-yl)amino)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methyl)(methyl)amino)propyl)isoindoline-1,3-dione (0.22 g, 0.39 mmol) in ethyl orthoformate (2.3 mL, 14 mmol) was treated with acetic acid (8 drops) and heated at reflux for 3.25 h; HPLC indicated nearly complete consumption of starting material. The reaction mixture was cooled to rt, diluted with toluene (10 mL), and concentrated in vacuo to remove most of the volatiles, and further concentrated under the flow of air. The resulting clear, dark brown oil was purified by column chromatography (2×22 cm silica; 0-1% 7 N NH3 in CH3OH/CH2Cl2) to afford the title compound (0.19 g, 85%) as a pale yellow foam: MS (ESI+) for C26H29ClN6O4 m/z 525.2 [M+H]+; HPLC purity 92% (ret. time, 2.917 min).

Workup

  1. temperatureheated
  2. temperatureat reflux for 3.25 h
  3. customconsumption of starting material
  4. additiondiluted with toluene (10 mL)
  5. concentrationconcentrated in vacuo
  6. customto remove most of the volatiles
  7. concentrationfurther concentrated under the flow of air
  8. customThe resulting clear, dark brown oil was purified by column chromatography (2×22 cm silica; 0-1% 7 N NH3 in CH3OH/CH2Cl2)

Sources & evidence

ORD record
ord-24ef15339e1147bb8577c1690fb69177
Source dataset
uspto-grants-2016_07
Patent number
US09394310B2

Reaction notes

Loading…