(4-Isopropoxy-phenyl)-carbamic acid 4-nitrophenyl ester → HCID 178458517, compound

HRID 657280Notes

Reaction equation

HRID 657280 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[C:23]3[C:18](=[CH:19][C:20]([O:24][CH2:25][CH2:26][CH2:27][C:28]4[NH:32][N:31]=[N:30][N:29]=4)=[CH:21][CH:22]=3)[N:17]=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])(C)(C)C.C(O)(C(F)(F)F)=O.C1(OC)C=CC=CC=1.[N+](C1C=CC(OC(=O)[NH:59][C:60]2[CH:65]=[CH:64][C:63]([O:66][CH:67]([CH3:69])[CH3:68])=[CH:62][CH:61]=2)=CC=1)([O-])=O>N1C=CC=CC=1>[CH:67]([O:66][C:63]1[CH:64]=[CH:65][C:60]([NH:59][C:6]([N:8]2[CH2:9][CH2:10][CH:11]([C:14]3[C:23]4[C:18](=[CH:19][C:20]([O:24][CH2:25][CH2:26][CH2:27][C:28]5[NH:32][N:31]=[N:30][N:29]=5)=[CH:21][CH:22]=4)[N:17]=[CH:16][N:15]=3)[CH2:12][CH2:13]2)=[O:7])=[CH:61][CH:62]=1)([CH3:69])[CH3:68]

Participants

5

Reactant 3

HCID 58769998(4-Isopropoxy-phenyl)-carbamic acid 4-nitrophenyl esterHCID 66633105Anisole trifluoroacetic acidHCID 178451806HCID 178451806, compound

Product 1

HCID 178458517HCID 178458517, compoundYield 14%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 4-{7-[3-(1H-Tetrazol-5-yl)-propoxy]-quinazolin-4-yl}-piperidine-1-carboxylic acid tert-butyl ester (6.1 mg, 14 μmol), as prepared in the previous step, in 9:1 TFA/anisole (100 μL) was stirred at 100° C. for 10 min. The solution was then concentrated. Pyridine (100 μL) and (4-isopropoxy-phenyl)-carbamic acid 4-nitro-phenyl ester (5.8 mg, 18 μmol), as prepared in Example 1a, were added, and the solution was stirred at 80° C. for 15 min. The reaction was concentrated, taken up in 1M NaH2PO4 (2 mL), and extracted with 95:5 DCM/MeOH (2×2 mL). The combined organic layers were dried (Na2SO4), concentrated, and purified by flash silica cartridge chromatography (EtOAc→acetone eluent) to provide the title compound (1.0 mg, 14%). 1H-NMR (400 MHz, 95:5 CDCl3/CD3OD) δ 9.09 (s, 1H), 8.08 (s, 1H), 7.30-7.21 (m, 4H), 6.85 (m, 2H), 4.49 (septet, 1H), 4.27 (m, 2H), 4.24 (t, 2H), 3.70 (tt, 1H), 3.19 (t, 2H), 3.12 (td, 2H), 2.40 (m, 2H), 2.17-1.92 (m, 4H), 1.32 (d, 6H). LC/MS (ESI) calcd mass 516.3, found 517.2 (MH)+.

Workup

  1. concentrationThe solution was then concentrated
  2. additionwere added
  3. stirringthe solution was stirred at 80° C. for 15 min
  4. concentrationThe reaction was concentrated
  5. extractionextracted with 95:5 DCM/MeOH (2×2 mL)
  6. dry with materialThe combined organic layers were dried (Na2SO4)
  7. concentrationconcentrated
  8. custompurified by flash silica cartridge chromatography (EtOAc→acetone eluent)

Sources & evidence

ORD record
ord-ec7496e585624d2c83c1c0c6cadca49a
Source dataset
uspto-grants-2011_12
Patent number
US08071768B2

Reaction notes

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