Phthalimide → 6-((1,3-Dioxoisoindolin-2-yl)methyl)-2-(4-phenoxyphenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide

HRID 64364Notes

Reaction equation

HRID 64364 reaction equation
[C:1]1(=[O:11])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3](=[O:10])[NH:2]1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O[CH2:32][CH:33]1[CH2:38][N:37]2[N:39]=[C:40]([C:45]3[CH:50]=[CH:49][C:48]([O:51][C:52]4[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=4)=[CH:47][CH:46]=3)[C:41]([C:42]([NH2:44])=[O:43])=[C:36]2[NH:35][CH2:34]1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[O:11]=[C:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3](=[O:10])[N:2]1[CH2:32][CH:33]1[CH2:38][N:37]2[N:39]=[C:40]([C:45]3[CH:50]=[CH:49][C:48]([O:51][C:52]4[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=4)=[CH:47][CH:46]=3)[C:41]([C:42]([NH2:44])=[O:43])=[C:36]2[NH:35][CH2:34]1

Participants

6

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 1369281156-(Hydroxymethyl)-2-(4-phenoxyphenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide

Product 1

HCID 1369280806-((1,3-Dioxoisoindolin-2-yl)methyl)-2-(4-phenoxyphenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamideYield 81.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of isoindoline-1,3-dione (74 mg, 0.5 mmol) in THF (20 mL) was added PPh3 (393 mg, 1.5 mmol) and 6-(hydroxymethyl)-2-(4-phenoxyphenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide (180 mg, 0.5 mmol). DIAD (253 mg, 1.25 mmol) was added dropwise at 0° C. and stirred for 10 min. The mixture was allowed to warm to it and stirred for 16 hr. Concentrated and purified by chromatography column on 5 g of silica gel eluting with DCM/CH3OH to afford 200 mg (62%) of 6-((1,3-dioxoisoindolin-2-yl)methyl)-2-(4-phenoxyphenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide as a yellow solid. MS (ESI) m/e [M+1]+ 493.9.

Workup

  1. temperatureto warm to it
  2. stirringstirred for 16 hr
  3. concentrationConcentrated
  4. custompurified by chromatography column on 5 g of silica gel eluting with DCM/CH3OH

Sources & evidence

ORD record
ord-b4dc2d918dc64da1928f530683125a2f
Source dataset
uspto-grants-2016_09
Patent number
US09447106B2

Reaction notes

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