1,1'-Carbonyldiimidazole → HCID 71002255, compound

HRID 2281076Notes

Reaction equation

HRID 2281076 reaction equation
[Cl:1][C:2]1[C:10]2[N:9]=[N:8][N:7]([CH2:11][CH:12]3[CH2:14][CH2:13]3)[C:6]=2[CH:5]=[CH:4][C:3]=1[C:15]1[CH:20]=[CH:19][C:18]([CH2:21][NH2:22])=[CH:17][CH:16]=1.[C:23](N1C=CN=C1)(N1C=CN=C1)=[O:24].Cl.[NH2:36][CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39]>ClCCl>[Cl:1][C:2]1[C:10]2[N:9]=[N:8][N:7]([CH2:11][CH:12]3[CH2:14][CH2:13]3)[C:6]=2[CH:5]=[CH:4][C:3]=1[C:15]1[CH:16]=[CH:17][C:18]([CH2:21][NH:22][C:23]([NH:36][CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39])=[O:24])=[CH:19][CH:20]=1

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 2723640Glycine ethyl ester, hydrochlorideHCID 70978065HCID 70978065, compound

Product 1

HCID 71002255HCID 71002255, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

1-{4-[4-Chloro-1-(cyclopropylmethyl)-1H-benzotriazol-5-yl]phenyl}methanamine (58 mg, 1.8 mmol) was dissolved in dichloromethane (1.8 mL) and treated with carbonyldiimidazole (0.15 g, 0.93 mmol, 5 equiv). The mixture was stirred at ambient temperatures for 2 hours and then treated with ethyl aminoacetate hydrochloride (0.26 g, 1.8 mmol, 10 equiv). The mixture was stirred until complete, diluted with dichloromethane (30 mL) and washed with sodium bicarbonate (2×30 mL, aqueous saturated). The organic layer was dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by preparative reverse phase HPLC (85:15 to 35:65; water containing 0.1% trifluoroacetic acid:acetonitrile containing 0.1% trifluoroacetic acid) to afford the titled compound: 1H-NMR (400 MHz, CDCl3) δ 7.53-7.40 (6H, m); 4.55 (2H, dd, J=6.9, 3.8 Hz); 4.49 (2H, m); 4.25-4.17 (2H, m); 4.02 (2H, s); 1.47-1.38 (1H, m); 1.27 (3H, t, J=6.6 Hz); 0.71-0.66 (2H, m); 0.54-0.49 (2H, m) ppm; high resolution mass spectrometry (ES+) m/z 442.1660 [(M+H)+; calculated for C22H25ClN5O3: 442.1640].

Workup

  1. stirringThe mixture was stirred until complete,
  2. washwashed with sodium bicarbonate (2×30 mL, aqueous saturated)
  3. dry with materialThe organic layer was dried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by preparative reverse phase HPLC (85:15 to 35:65; water containing 0.1% trifluoroacetic acid:acetonitrile containing 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-44ca95e3752c41a28852f967b0359060
Source dataset
uspto-grants-2015_09
Patent number
US09139576B2

Reaction notes

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