tert-Butanol → HCID 22668308, compound

HRID 381776Notes

Reaction equation

HRID 381776 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17](O)=[O:18])=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:20]1[C:21](=[O:30])[NH:22][C:23]2[C:28]([CH:29]=1)=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:38])C=CC=CC=1.C([N:50]([CH2:53]C)CC)C.[CH3:55][C:56]([OH:59])([CH3:58])[CH3:57]>>[C:56]([O:59][C:53]([NH:50][C:17]([C:13]1[CH:12]=[C:11]2[C:16](=[CH:15][CH:14]=1)[N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:7])[C:9]([C:20]1[C:21](=[O:30])[NH:22][C:23]3[C:28]([CH:29]=1)=[CH:27][CH:26]=[CH:25][CH:24]=3)=[CH:10]2)=[O:18])=[O:38])([CH3:58])([CH3:57])[CH3:55]

Participants

5

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 22668334HCID 22668334, compound

Product 1

HCID 22668308HCID 22668308, compound

Conditions

Temperature
100 °C

Procedure

A solution of 1-(tert-butoxycarbonyl)-2-(2-oxo-1,2-dihydro-3-quinolinyl)-1-H-indole-5-carboxylic acid (6-1, 0.200 mg, 0.49 mmol, 1 equiv), diphenylphosphoryl azide (128 μL, 0.59 mmol, 1.2 equiv), and triethylamine (89 μL, 0.64 mmol, 1.3 equiv) in t-BuOH (30 mL) was heated at 100° C. for 2 h. Cuprous chloride (4.9 mg, 0.05 mmol, 0.1 equiv) was added and the resulting mixture was heated at 100° C. for 24 h. The solution was concentrated, and the residue was partitioned between and saturated aqueous NaHCO3 solution (75 mL) and EtOAc (3×60 mL). The combined organic layers were washed once with water (150 mL) then brine (150 mL) and dried over sodium sulfate and concentrated. The residue was purified by reverse-phase liquid chromatography (H2O/CH3CN gradient with 0.1% TFA present) to provide tert-butyl 5-[(tert-butoxycarbonyl)amino]-2-(2-oxo-1,2-dihydro-3-quinolinyl)-1H-indole-1-carboxylate (9-1). 1H NMR (500 MHz, DMSO-d6) δ12.06 (s, 1H), 9.37 (bs, 1H), 8.05 (s, 1H), 7.92 (d, 1H, J=7.8 Hz), 7.82 (s, 1H), 7.52 (m, 2H), 7.35 (m, 2H), 7.21 (m, 2H), 6.72 (s, 1H), 1.50 (s, 9H), 1.34 (s, 9H).

Workup

  1. concentrationThe solution was concentrated
  2. customthe residue was partitioned between and saturated aqueous NaHCO3 solution (75 mL) and EtOAc (3×60 mL)
  3. washThe combined organic layers were washed once with water (150 mL)
  4. dry with materialbrine (150 mL) and dried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by reverse-phase liquid chromatography (H2O/CH3CN gradient with 0.1% TFA present)

Sources & evidence

ORD record
ord-a7e8c9ae72c04fa097d2f6c07100ad3b
Source dataset
uspto-grants-2001_10
Patent number
US06306874B1

Reaction notes

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