1,1'-Carbonyldiimidazole → HCID 178426294, compound

HRID 251197Notes

Reaction equation

HRID 251197 reaction equation
Br.[CH:2]([C:5]1[C:6]([CH2:11][N:12]([CH2:20][C:21]2[C:26]([CH3:27])=[CH:25][CH:24]=[CH:23][N:22]=2)[CH:13]2[CH2:18][CH2:17][CH:16]([NH2:19])[CH2:15][CH2:14]2)=[N:7][CH:8]=[CH:9][CH:10]=1)([CH3:4])[CH3:3].[C:28]([N:35]1C=CN=C1)(N1C=CN=C1)=[O:29].N[OH:41].Cl.CCN(C(C)C)C(C)C>C1COCC1.CN(C=O)C>[CH:2]([C:5]1[C:6]([CH2:11][N:12]([CH2:20][C:21]2[C:26]([CH3:27])=[CH:25][CH:24]=[CH:23][N:22]=2)[C@H:13]2[CH2:14][CH2:15][C@H:16]([NH:19][C:28]([NH:35][OH:41])=[O:29])[CH2:17][CH2:18]2)=[N:7][CH:8]=[CH:9][CH:10]=1)([CH3:4])[CH3:3]

Participants

7

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 443297Hydroxyamine hydrochlorideHCID 131728608HCID 131728608, compound

Product 1

HCID 178426294HCID 178426294, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of COMPOUND 117 (159 mg, 0.45 mmol) and 1,1′-carbonyl-diimidazole (73 mg, 0.45 mmol) in anhydrous THF (5 mL) was stirred at room temperature, under a N2 atmosphere, for 45 minutes. The mixture was concentrated on a rotary evaporator. To the resultant residue were added DMF (3 mL), NH2OH.HCl (125 mg, 1.8 mmol), and DIPEA (0.40 mL, 2.3 mmol). The mixture was stirred for 16 hours and concentrated. The colorless oily residue was dissolved in EtOAc (15 mL), washed with brine (4×10 mL), dried over Na2SO4, and concentrated. Purification of the crude material by silica gel column chromatography (10 g silica, eluted with 10% NH4OH/10% MeOH/CH2Cl2) provided COMPOUND 351 (85 mg, 46%), as a white solid. 1H NMR (CDCl3) δ 0.91 (d, 6H, J=7.5 Hz), 1.01-1.16 (m, 2H), 1.59-1.70 (m, 2H), 1.97 (d, 2H, J=11.5 Hz), 2.18 (d, 2H, J=11.5 Hz), 2.21 (s, 3H), 2.44 (t, 1H, J=10.5 Hz), 2.71-2.80 (m, 1H), 3.58-3.70 (m, 1H), 3.79 (s, 4H), 5.82 (d, 1H, J=8.0 Hz), 6.60 (s, 1H), 7.10-7.18 (m, 2H), 7.45 (d, 1H, J=7.5 Hz), 7.53 (dd, 1H, J=8.0, 1.5 Hz), 8.35 (ddd, 2H, J=12.5, 5.0, 1.5 Hz), 9.94 (s br, 1H); 13C NMR (CDCl3) δ 18.57, 23.52(2), 26.40 (2), 27.39, 33.71(2), 49.12, 53.81, 54.31, 58.24, 123.07, 123.51, 134.19, 134.60, 138.67, 144.95, 145.85(2), 146.28 (2), 161.77; ES-MS m/z 412 (M+H). Anal. Calcd. For C23H33N5O2.0.1H2O: C, 66.83; H, 8.10; N, 16.94. Found: C, 66.63; H, 8.18; N, 16.94.

Workup

  1. concentrationThe mixture was concentrated on a rotary evaporator
  2. concentrationconcentrated
  3. dissolutionThe colorless oily residue was dissolved in EtOAc (15 mL)
  4. washwashed with brine (4×10 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customPurification of the crude material
  8. washby silica gel column chromatography (10 g silica, eluted with 10% NH4OH/10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-e21d5a069f094486a1318a83e6825bfe
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

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