Diisopropylcarbodiimide → HCID 58858090, compound

HRID 1916369Notes

Reaction equation

HRID 1916369 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:16][C:15]3[C:14](=[O:17])[N:13]([C:18]4[CH:23]=[CH:22][C:21]([O:24][CH2:25][C:26]([OH:29])([CH3:28])[CH3:27])=[C:20]([CH2:30][CH3:31])[CH:19]=4)[CH:12]=[N:11][C:10]=3[CH:9]=2)=[CH:4][CH:3]=1.N1(C2C=CN=CC=2)CCCC1.[C:43]([O:47][C:48]([NH:50][CH2:51][C:52](O)=[O:53])=[O:49])([CH3:46])([CH3:45])[CH3:44].C(N=C=NC(C)C)(C)C.O.NN>C(Cl)Cl>[C:43]([O:47][C:48]([NH:50][CH2:51][C:52]([O:29][C:26]([CH3:27])([CH3:28])[CH2:25][O:24][C:21]1[CH:22]=[CH:23][C:18]([N:13]2[C:14](=[O:17])[C:15]3[S:16][C:8]([C:5]4[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=4)=[CH:9][C:10]=3[N:11]=[CH:12]2)=[CH:19][C:20]=1[CH2:30][CH3:31])=[O:53])=[O:49])([CH3:46])([CH3:45])[CH3:44]

Participants

7

Reactant 5

HCID 12734Diisopropylcarbodiimide2×HCID 24654Hydrazine hydrate (1:1)HCID 755674-PyrrolidinopyridineHCID 78288N-(tert-butoxycarbonyl)glycine2×HCID 16718656HCID 16718656, compound

Product 1

HCID 58858090HCID 58858090, compoundYield 106.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 6-(4-chlorophenyl)-3-(3-ethyl-4-(2-hydroxy-2-methylpropoxy)-phenyl)thieno[3,2-d]pyrimidin-4(3H)-one (0.96 g, 2.11 mmol), 4-pyrrolidinopyridine (0.31 g, 2.11 mmol) and N-(tert-butoxycarbonyl)glycine (1.11 g, 6.33 mmol) in 20 mL of CH2Cl2 heated at reflux was added diisopropylcarbodiimide (0.98 mL; 6.33 mmol) over 3 h via syringe pump. The suspension was heated at reflux for 1 h and additional N-(tert-butoxycarbonyl)glycine (0.55 g, 3.17 mmol) was added followed by diisopropylcarbodiimide (0.55 mL, 3.17 mmol) over 2 hrs via syringe pump. The suspension heated at reflux for 1 h and cooled to rt. Hydrazine monohydrate (0.34 mL, 7.01 mmol) was added and the suspension stirred at rt for 2 h. The suspension was cooled to 0° C., filtered and the filtrate washed with cold, 1N HCl, cold, dilute NaHCO3 solution, dried over anhydrous MgSO4, filtered and the filtrate concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, EtOAc/Hexanes, 0:100 to 1:1 gradient) to afford 1.37 g (100%) of the title compound as an off-white solid. 1H NMR (CDCl3) δ 1.24 (t, 3H), 1.45 (s, 9H), 1.64 (s, 6H), 2.68-2.73 (m, 2H), 3.85 (d, J=4.95 Hz, 2H), 4.18 (s, 2H), 4.98 (br s, 1H), 6.92 (d, J=9.35 Hz, 1H), 7.20-7.22 (m, 2H), 7.44 (d, J=8.79 Hz, 2H), 7.53 (s, 1H), 7.66 (d, J=8.25 Hz, 2H), 8.13 (s, 1H); 13C NMR (CDCl3) δ 13.68, 23.39, 23.67, 28.28, 42.87, 72.72, 79.86, 81.86, 111.48, 120.82, 123.25, 125.42, 127.62, 129.42, 129.67, 131.54, 134.25, 135.59, 148.29, 151.50, 155.58, 156.69, 156.92, 157.37, 169.47; HPLC (Method #1) 4.80 min retention time; LCMS (ES): m/z 612 [M+H]+.

Workup

  1. temperatureat reflux
  2. temperatureThe suspension was heated
  3. temperatureat reflux for 1 h
  4. temperatureThe suspension heated
  5. temperatureat reflux for 1 h
  6. temperatureThe suspension was cooled to 0° C.
  7. filtrationfiltered
  8. washthe filtrate washed with cold, 1N HCl
  9. dry with materialcold, dilute NaHCO3 solution, dried over anhydrous MgSO4
  10. filtrationfiltered
  11. concentrationthe filtrate concentrated under reduced pressure
  12. customThe residue was purified by flash chromatography (silica gel, EtOAc/Hexanes, 0:100 to 1:1 gradient)

Sources & evidence

ORD record
ord-d0ffe591345748d0a2151daacdc95b07
Source dataset
uspto-grants-2013_12
Patent number
US08618115B2

Reaction notes

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