Sodium Carbonate → HCID 68158136, compound

HRID 243269Notes

Reaction equation

[F:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:3]=1.[C:16]([O:20][C:21]([NH:23][CH2:24][C:25](O)=[O:26])=[O:22])([CH3:19])([CH3:18])[CH3:17].C1C=NC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.C([O-])(O)=O.[Na+].C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl.CN(C=O)C.O>[C:16]([O:20][C:21](=[O:22])[NH:23][CH2:24][C:25](=[O:26])[NH:6][C:5]1[CH:7]=[CH:8][C:2]([F:1])=[CH:3][C:4]=1[NH:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)([CH3:19])([CH3:17])[CH3:18]

Participants

Conditions

Temperature: 0 °C

Procedure

To a mixture of 4-fluoro-2-phenylaminoaniline (3.0 g, 14.85 mmol), tert-butoxycarbonyl glycine (2.4 g, 15 mmol) and HOAt (0.68 g, 5 mmol) in DCM (20 mL) and DMF (1 mL) at 0° C. was added EDCI (2.88 g, 15 mmol). The mixture was stirred at 0° C. for 1 h. To the reaction mixture was added a saturated aqueous solution of NaHCO3 (20 mL), saturated aqueous solution of Na2CO3 (10 mL) and water (10 mL). The mixture was extracted with DCM (2×20 mL) and the combined organic layers were dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-8% MeOH in DCM) to afford the title compound as a brown gum, (4.79 g, 89%). 1H NMR δ (ppm) (CHCl3-d): 7.95 (1H, s), 7.50 (1H, dd, J=8.83, 5.91 Hz), 7.32-7.22 (2H, m), 6.98-6.97 (4H, m), 6.68 (1H, dt, J=8.6, 2.7 Hz), 6.05 (1H, s), 5.06 (1H, s), 3.89 (2H, d, J=5.92 Hz), 1.42 (9H, s)

Workup

extractionThe mixture was extracted with DCM (2×20 mL)
dry with materialthe combined organic layers were dried (Na2SO4)
concentrationconcentrated in vacuo
customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-8% MeOH in DCM)

Sources & evidence

ORD record: ord-f59435a68c614018a1d41ff6ef8e1786
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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