Sodium hydride → HCID 59394165, compound

HRID 45092Notes

Reaction equation

HRID 45092 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([O:10][C:11]3[C:12]4[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][C:13]=4[N:14]=[CH:15][N:16]=3)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[H-].[Na+].[C:30](Cl)(=[O:41])[O:31][C:32]1[CH:37]=[CH:36][C:35]([N+:38]([O-:40])=[O:39])=[CH:34][CH:33]=1>C1COCC1>[N+:38]([C:35]1[CH:36]=[CH:37][C:32]([O:31][C:30]([N:1]2[C:9]3[C:4](=[CH:5][C:6]([O:10][C:11]4[C:12]5[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][C:13]=5[N:14]=[CH:15][N:16]=4)=[CH:7][CH:8]=3)[CH:3]=[CH:2]2)=[O:41])=[CH:33][CH:34]=1)([O-:40])=[O:39]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 821294-Nitrophenyl chloroformateHCID 59394410HCID 59394410, compound

Product 1

HCID 59394165HCID 59394165, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of tert-butyl 4-(1H-indol-5-yloxy)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8 H)-carboxylate, Example 31-C, (1 g, 2.73 mmol) in 20 mL of THF, sodium hydride (0.164 g, 4.09 mmol, 60% in mineral oil) is added at 0° C. After 1.5 h, a solution of 4-nitrophenyl carbonochloridate (1.65 g, 8.19 mmol) in THF (10 mL) is added. The mixture is allowed to warm to rt and stir overnight before being quenched with ice water and extracted with EtOAc. The combined organic layers are washed with water and brine before being dried (Na2SO4) and concentrated. The residue is then separated by FCC (20-80% EtOAc/heptane) to give the title compound. 1H NMR (400 MHz, CDCl3) δ ppm 8.54 (s, 1 H), 8.34-8.43 (m, 2 H), 7.79 (d, J=3.8 Hz, 1 H), 7.49-7.57 (m, 2 H), 7.41 (d, J=2.3 Hz, 1 H), 7.17 (dd, J=9.0, 2.4 Hz, 1 H), 6.75 (d, J=3.5 Hz, 1 H), 5.31 (s, 1 H), 4.65 (s, 2 H), 3.80 (t, J=5.8 Hz, 2 H), 2.95 (t, J=5.6 Hz, 2 H), 1.53 (s, 9 H).

Workup

  1. custombefore being quenched with ice water
  2. extractionextracted with EtOAc
  3. washThe combined organic layers are washed with water and brine
  4. dry with materialbefore being dried (Na2SO4)
  5. concentrationconcentrated
  6. customThe residue is then separated by FCC (20-80% EtOAc/heptane)

Sources & evidence

ORD record
ord-6e590f77b4f243fb92f7dcfa23afb1eb
Source dataset
uspto-grants-2013_09
Patent number
US08541432B2

Reaction notes

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