Potassium Carbonate → ethyl 2-(1-((tert-butoxycarbonyl)amino)cyclopropyl)-5-(3-(tert-butylamino)-6-fluoro-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylate

HRID 1056148Notes

Reaction equation

HRID 1056148 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([C:11]1[NH:12]C(C2C=CC=C3C=2N=C(NCC(F)(F)F)C(C)=N3)=C[C:15]=1[C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[CH2:39][C:40]([C:42]1[C:51]([F:52])=[CH:50][CH:49]=[C:48]2[C:43]=1[N:44]=[C:45]([NH:54][C:55]([CH3:58])([CH3:57])[CH3:56])[C:46]([CH3:53])=[N:47]2)=O.[C:59](OC(NC1(C(=O)CC(OCC)=O)CC1)=O)(C)(C)C.C([O-])([O-])=O.[K+].[K+]>CCO.C1COCC1.CC(O)=O>[C:1]([O:5][C:6]([NH:8][C:9]1([C:11]2[NH:12][C:40]([C:42]3[C:51]([F:52])=[CH:50][CH:49]=[C:48]4[C:43]=3[N:44]=[C:45]([NH:54][C:55]([CH3:58])([CH3:57])[CH3:56])[C:46]([CH3:53])=[N:47]4)=[CH:39][C:15]=2[C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:10][CH2:59]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 897819262-Bromo-1-(3-(tert-butylamino)-6-fluoro-2-methylquinoxalin-5-yl)ethanoneHCID 89781999Ethyl 3-(1-{[(tert-butoxy)carbonyl]amino}cyclopropyl)-3-oxopropanoateHCID 89783413ethyl 2-(1-((tert-butoxycarbonyl)amino)ethyl)-5-(2-methyl-3-((2,2,2-trifluoroethyl)amino)quinoxalin-5-yl)-1H-pyrrole-3-carboxylate

Product 1

HCID 89783968ethyl 2-(1-((tert-butoxycarbonyl)amino)cyclopropyl)-5-(3-(tert-butylamino)-6-fluoro-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylateYield 58%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 702EthanolSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

This compound (230 mg, 0.44 mmol, 58% yield) as a yellow foam was prepared according to the procedures described for Intermediate 293b, using 2-bromo-1-(3-(tert-butylamino)-6-fluoro-2-methylquinoxalin-5-yl)ethanone (605) (268 mg, 0.76 mmol), ethyl 3-(1-((tert-butoxycarbonyl)amino)cyclopropyl)-3-oxopropanoate (604) (619 mg, 2.28 mmol) and K2CO3 (525 mg, 3.80 mmol) in EtOH (2 mL) and THF (2 mL) was stirred at RT for 2 days, followed by subsequent treatment of the resulting 295a (light-yellow oil, m/z (ESI, +ve) 545.2 (M+H)+) with NH4OAc (469 mg, 6.08 mmol) in EtOH (5 mL) and HOAc (3 mL) at 60° C. for 18 h. 1H NMR (400 MHz, CDCl3) δ ppm 7.64 (dd, J=8.90, 5.97 Hz, 1H), 7.17 (dd, J=11.74, 9.00 Hz, 1H), 4.86 (s, 1H), 4.34 (q, J=7.04 Hz, 2H), 2.52 (s, 3H), 1.64 (s, 9H), 1.40 (t, J=7.14 Hz, 3H), 1.36 (s, 9H), 1.20-1.33 (m, 4H). 19F NMR (376 MHz, CDCl3) δ ppm −109.93 (s, 1F). m/z (ESI, +ve) 526.2 (M+H)+.

Sources & evidence

ORD record
ord-bfa49b5749614c4d941dae66bae5b5ed
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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