Hydrochloric Acid → 1-({2-(Hex-5-enyl-methyl-carbamoyl)-4-[2-(4-isopropyl-thiazol-2-yl)-quinazolin-4-yloxy]-cyclopentanecarbonyl}-amino)-2-vinyl-cyclopropanecarboxylic acid

HRID 1443436Notes

Reaction equation

HRID 1443436 reaction equation
[CH2:1]([N:7]([CH3:27])[C:8]([CH:10]1[CH2:14][CH:13]([OH:15])[CH2:12][CH:11]1[C:16]([NH:18][C:19]1([C:24]([OH:26])=[O:25])[CH2:21][CH:20]1[CH:22]=[CH2:23])=[O:17])=[O:9])[CH2:2][CH2:3][CH2:4][CH:5]=[CH2:6].[H-].[Na+].Cl[C:31]1[C:40]2[C:35](=[CH:36][C:37](OC)=[CH:38][CH:39]=2)[N:34]=[C:33]([C:43]2[S:44][CH:45]=[C:46]([CH:48]([CH3:50])[CH3:49])[N:47]=2)[N:32]=1.Cl>C1COCC1.CCOC(C)=O>[CH2:1]([N:7]([CH3:27])[C:8]([CH:10]1[CH2:14][CH:13]([O:15][C:31]2[C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[N:34]=[C:33]([C:43]3[S:44][CH:45]=[C:46]([CH:48]([CH3:50])[CH3:49])[N:47]=3)[N:32]=2)[CH2:12][CH:11]1[C:16]([NH:18][C:19]1([C:24]([OH:26])=[O:25])[CH2:21][CH:20]1[CH:22]=[CH2:23])=[O:17])=[O:9])[CH2:2][CH2:3][CH2:4][CH:5]=[CH2:6]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 591654744-Chloro-7-methoxy-2-[4-(propan-2-yl)-1,3-thiazol-2-yl]quinazolineHCID 668702741-{[2-(Hex-5-enylmethylcarbamoyl)-4-hydroxycyclopentanecarbonyl]amino}-2-vinylcyclopropanecarboxylic acid

Product 1

HCID 684096781-({2-(Hex-5-enyl-methyl-carbamoyl)-4-[2-(4-isopropyl-thiazol-2-yl)-quinazolin-4-yloxy]-cyclopentanecarbonyl}-amino)-2-vinyl-cyclopropanecarboxylic acidYield 78%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Compound 37 (26 mg, 70 μmol) was dissolved in THF (3 mL, dried with mol. siev.). To this solution was added NaH (60% in oil, 8.2 mg, 210 μmol) and the reaction was incubated for 10 min at ambient temperature. To the reaction mixture was then added compound 39 (17.6 mg, 61 μmol) followed by incubation at ambient temperature for 16 h. To the reaction was then added 0.1 M HCl (aq) and EtOAc, the phases separated and the aqueous phase extracted with another portion of EtOAc. The pooled organic phases were dried (MgSO4), filtered and concentrated in vacuo which gave a crude product which was further purified by flash-chromatography (Silica; DCM:MeOH) to afford the title compound (30 mg, 78%). LC/MS>95%, m/z (ESI+)=632 (MH+).

Workup

  1. customthe phases separated
  2. extractionthe aqueous phase extracted with another portion of EtOAc
  3. dry with materialThe pooled organic phases were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo which
  6. customgave a crude product which
  7. customwas further purified by flash-chromatography (Silica; DCM:MeOH)

Sources & evidence

ORD record
ord-22035a8f7ec3439ab6fd235646400789
Source dataset
uspto-grants-2010_02
Patent number
US07659245B2

Reaction notes

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