Dichloromethane → HCID 136065296, compound

To a round-bottomed flask containing the tetrafluoroborate salt (propargyl)Co2(CO)6+BF4− (0.271 g, 0.66 mmol) was added anhydrous dichloromethane (dried by distillation over P2O5; 22 ml). The nearly clear red dark solution was stirred at room temperature for few minutes under argon, then tert-butyl 4-{N-[(6RS)-2-methoxymethyl-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl]amino}benzoate (0.215 g, 0.51 mmol) was added in one portion. Stirring was continued at this temperature for 5 min then diisopropylethylamine (0.18 ml, 1.04 mmol) was added and the reaction mixture was stirred at room temperature for 45 min under argon. The reaction mixture was partitioned between ethyl acetate (150 ml) and brine (60 ml). The aqueous layer was extracted with more ethyl acetate (2×50 ml). The combined extracts were washed with 10% aqueous citric acid (50 ml), brine (50 ml), dried (Na2SO4), and concentrated in vacuo. Purification by column chromatography, on elution with 40% ethyl acetate in dichloromethane, gave a red solid: 0.285 g (75%). To a solution of this complex (0.267 g, 0.36 mmol) in ethanol (60 ml) was added Fe(NO3)3.9H2O (˜8.0 g). The clear solution was stirred at room temperature for 10 min then a second portion of Fe(NO3)3.9H2O (˜4.0 g) was added. The reaction mixture was stirred at room temperature for a longer 5 min then a final portion of Fe(NO3)3.9H2O (˜5.0 g) was added; the nearly clear solution was turned into a dark red mixture. Stirring was continued at room temperature for an extra 25 min, then the reaction mixture was partitioned between ethyl acetate (150 ml) and dilute brine (700 ml). The aqueous layer was extracted with more ethyl acetate (2×70 ml). The combined organics were washed with brine (3×70 ml), dried (Na2SO4), and concentrated in vacuo. Purification by column chromatography, on elution with 2% methanol in dichloromethane, afforded a white solid which was reprecipitated from dichloromethane/hexane; 0.122 g (74%), m.p. 191-192° C.; 1H-NMR (250 MHz, DMSO-d6, TMS) 1.51 (s, 9H, C(CH3)3), 2.23, 2.53 (m-obscured by DMSO peak) (2×m, each 1H, 7-H), 2.95-3.20 (m, 3H, C═CH, 8-H), 3.34 (s (obscured by the H2O peak), 3H, OCH3), 3.96 (ABq, J=18.0 Hz, 2H, CH2C≡C), 4.31 (s, 2H, 2-CH2), 5.79 (t, J=7.0 Hz. 1H, 6-H), 7.02 (d, J=9.01 Hz, 2H, 3′,5′-H). 7.58, 7.80 (2×s, each 1H, 5-H, 9-H), 7.76 (d, J=8.45 Hz, 2′,6′-H), 12.17 (s, 1H, N3—H); MS (ESI, m/z) 482 {(M+Na)+, 10%}; Found: C, 70-32; H, 6.31; N, 9.09; C27H29N3O4 requires C, 70.57; H, 6.36; N, 9.14%.

1. stirringStirring
2. stirringthe reaction mixture was stirred at room temperature for 45 min under argon
3. customThe reaction mixture was partitioned between ethyl acetate (150 ml) and brine (60 ml)
4. extractionThe aqueous layer was extracted with more ethyl acetate (2×50 ml)
5. washThe combined extracts were washed with 10% aqueous citric acid (50 ml), brine (50 ml)
6. dry with materialdried (Na2SO4)
7. concentrationconcentrated in vacuo
8. customPurification by column chromatography
9. washon elution with 40% ethyl acetate in dichloromethane
10. customgave a red solid
11. stirringThe clear solution was stirred at room temperature for 10 min
12. stirringThe reaction mixture was stirred at room temperature for a longer 5 min
13. stirringStirring
14. waitwas continued at room temperature for an extra 25 min
15. customthe reaction mixture was partitioned between ethyl acetate (150 ml) and dilute brine (700 ml)
16. extractionThe aqueous layer was extracted with more ethyl acetate (2×70 ml)
17. washThe combined organics were washed with brine (3×70 ml)
18. dry with materialdried (Na2SO4)
19. concentrationconcentrated in vacuo
20. customPurification by column chromatography
21. washon elution with 2% methanol in dichloromethane
22. customafforded a white solid which
23. customwas reprecipitated from dichloromethane/hexane

ORD record

ord-d9cedea112304075b8cb0786cc81e007

Source dataset

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07863284B2