Ethylorthoformate → HCID 86705751, compound

HRID 1054536Notes

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

Conditions

Temperature: 130 °C

Procedure

A solution of 2-(3-((((3aR,4S,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 (180 mg, 0.35 mmol) in ethyl orthoformate (5.8 mL, 35 mmol) was treated with acetic acid (4 drops) and heated at 130° C. for 7 hours. The reaction was cooled to room temperature and stirring was continued overnight. The reaction was concentrated and purified by flash chromatography (7N NH3 in MeOH/DMC 4:96) to yield 2-(3-((((3aR,4S,6R,6aS)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methyl)(methyl)amino)propyl)isoindoline-1,3-dione (165 mg, 90%) as a thick light brown syrup. MS (ESI+) for C26H29ClN6O4 m/z 525.4 [M+H]+.

Workup

temperatureThe reaction was cooled to room temperature
concentrationThe reaction was concentrated
custompurified by flash chromatography (7N NH3 in MeOH/DMC 4:96)

Sources & evidence

ORD record: ord-80cd7bb710f04751aef4be9d491d18d8
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394310B2

Reaction notes

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