Phthalimide → HCID 131736920, compound

HRID 56389Notes

Reaction equation

HRID 56389 reaction equation
C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.[C:34]1(=[O:44])[NH:38][C:37](=[O:39])[C:36]2=[CH:40][CH:41]=[CH:42][CH:43]=[C:35]12.[Cl:45][C:46]1[C:51]([O:52][CH3:53])=[CH:50][C:49]([O:54][CH3:55])=[C:48]([Cl:56])[C:47]=1[C:57]1[CH:58]=[C:59]2[C:64](=[CH:65][CH:66]=1)[N:63]=[C:62]([NH:67][C@H:68]1[C@H:72](O)[CH2:71][C@@H:70]([C:74]([O:76][CH3:77])=[O:75])[CH2:69]1)[N:61]=[CH:60]2>C1COCC1>[Cl:56][C:48]1[C:49]([O:54][CH3:55])=[CH:50][C:51]([O:52][CH3:53])=[C:46]([Cl:45])[C:47]=1[C:57]1[CH:58]=[C:59]2[C:64](=[CH:65][CH:66]=1)[N:63]=[C:62]([NH:67][C@H:68]1[C@@H:72]([N:38]3[C:34](=[O:44])[C:35]4[C:36](=[CH:40][CH:41]=[CH:42][CH:43]=4)[C:37]3=[O:39])[CH2:71][CH:70]([C:74]([O:76][CH3:77])=[O:75])[CH2:69]1)[N:61]=[CH:60]2

Participants

6

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 118036470(1S,3R,4R)-methyl 3-((6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)amino)-4-hydroxycyclopentanecarboxylate

Product 1

HCID 131736920HCID 131736920, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Ph3P (0.213 g, 0.812 mmol) was taken up in THF (6 ml) and cooled to −78° C. under N2. DIAD (0.126 ml, 0.650 mmol) was added followed by addition of phthalimide (0.105 g, 0.711 mmol) and stirred at −78° C. for 1 hour, followed by addition of (1S,3R,4R)-methyl 3-((6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)amino)-4-hydroxycyclopentanecarboxylate (0.100 g, 0.203 mmol) in 4 ml of THF at −78° C. The reaction was stirred overnight while warming to room temperature, after which the solvent was removed under reduced pressure. The residue was purified via flash chromatography (0-100% Hex/EtOAc; 12 g column) to afford methyl (3R,4S)-3-((6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)amino)-4-(1,3-dioxoisoindolin-2-yl)cyclopentane-1-carboxylate (0.126 g, 0.203 mmol). MS (ES+) C31H26Cl2N4O6 requires: 621, found: 622 [M+H]+.

Workup

  1. stirringThe reaction was stirred overnight
  2. temperaturewhile warming to room temperature
  3. customafter which the solvent was removed under reduced pressure
  4. customThe residue was purified via flash chromatography (0-100% Hex/EtOAc; 12 g column)

Sources & evidence

ORD record
ord-e9b708bc38924242854aa5cde021840e
Source dataset
uspto-grants-2016_09
Patent number
US09434700B2

Reaction notes

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