Hydrochloric Acid → HCID 57812517, compound

HRID 912050Notes

Reaction equation

HRID 912050 reaction equation
[OH:1][C:2]1[C:3]2[O:13][CH:12]=[C:11]([C:14]3[CH2:15][CH2:16][N:17]([C:20](OC(C)(C)C)=[O:21])[CH2:18][CH:19]=3)[C:4]=2[CH:5]=[N:6][C:7]=1[N+:8]([O-])=O.[Cl:27][C:28]1[C:33]([F:34])=[CH:32][CH:31]=[C:30]([Cl:35])[C:29]=1[CH:36](O)[CH3:37].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1COCC1.[N:63](C(OC(C)C)=O)=NC(OC(C)C)=O.C(O)C.Cl.C[Si](N=C=O)(C)C.CN(C=O)C.CCN(C(C)C)C(C)C>[Fe]>[NH2:8][C:7]1[N:6]=[CH:5][C:4]2[C:11]([C:14]3[CH2:15][CH2:16][N:17]([C:20]([NH2:63])=[O:21])[CH2:18][CH:19]=3)=[CH:12][O:13][C:3]=2[C:2]=1[O:1][CH:36]([C:29]1[C:30]([Cl:35])=[CH:31][CH:32]=[C:33]([F:34])[C:28]=1[Cl:27])[CH3:37]

Participants

12

Reactant 10

HCID 313Hydrochloric Acid2×HCID 702EthanolHCID 6228DimethylformamideHCID 8028TetrahydrofuranHCID 11776TriphenylphosphineHCID 70696Trimethylsilyl isocyanateHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 81531DiisopropylethylamineHCID 167700681-(2,6-Dichloro-3-fluorophenyl)ethan-1-olHCID 57812743HCID 57812743, compound2×

Product 1

HCID 57812517HCID 57812517, compound

Reagents, catalysts & solvents 1

HCID 23925IronCatalyst2×

Conditions

Temperature
40 °C

Procedure

To a solution of tert-butyl 4-(7-hydroxy-6-nitrofuro[3,2-c]pyridin-3-yl)-3,6-dihydro-2H-pyridine-1-carboxylate (Intermediate 14) (20.0 mg, 0.0553 mmol), 1-(2,6-dichloro-3-fluorophenyl)ethanol (34.7 mg, 0.166 mmol), and PPh3 (43.6 mg, 0.166 mmol) in THF (1.0 mL, 12 mmol) under nitrogen was added dropwise diisopropyl azodicarboxylate (22.4 mg, 0.111 mmol), and the mixture was heated at 40° C. overnight. THF was evaporated, and iron powder (30.9 mg, 0.553 mmol), ethanol (1.5 mL, 26 mmol) and 1 drop of aq. 12 M HCl were added. The mixture was stirred at 70° C. for 20 minutes. Iron was taken out by stirring bar. 5 drops of aq. 12 M HCl were added, and the mixture was stirred at 70° C. for 2 h, passed through SCX-2 SPE cartridge and eluted by 2 M NH3 in methanol. This material was completely dried in vacuo overnight. Trimethylsilyl isocyanate (11.2 μL, 0.0830 mmol), DMF (1.0 mL, 13 mmol) and DIPEA (19.3 μL, 0.111 mmol) were added, and the mixture was stirred at room temperature for 1 h. The reaction mixture was filtered and purified using the MDPS to give the title compound. MS (ES+): m/z 465.16/467.18 [MH+]. HPLC: tR=0.72 min (HPLC-ACQUITY, Analytical). 1H NMR (400 MHz, CD3OD): δ=1.88 (d, J=6.8 Hz, 3H), 2.45-2.56 (m, 2H), 3.64 (t, J=5.8 Hz, 2H), 4.10 (d, J=2.5 Hz, 2H), 6.26 (br. s., 1H), 6.50 (q, J=6.8 Hz, 1H), 7.22 (t, J=8.7 Hz, 1H), 7.40 (dd, J=9.0, 4.9 Hz, 1H), 7.66 (s, 1H), 8.19 (br. s., 1H).

Workup

  1. customTHF was evaporated
  2. stirringby stirring bar
  3. stirringthe mixture was stirred at 70° C. for 2 h
  4. washeluted by 2 M NH3 in methanol
  5. customThis material was completely dried in vacuo overnight
  6. stirringthe mixture was stirred at room temperature for 1 h
  7. filtrationThe reaction mixture was filtered
  8. custompurified

Sources & evidence

ORD record
ord-7673bd9d10684b89bc48f4229066316d
Source dataset
uspto-grants-2011_09
Patent number
US08022206B2

Reaction notes

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