1,1'-Carbonyldiimidazole → HCID 67540189, compound

HRID 1192447Notes

Reaction equation

HRID 1192447 reaction equation
C1N=CN(C(N2C=NC=C2)=O)C=1.C1C=C2N=NN(O)C2=CC=1.O.Cl.Cl.[N:26]1([C:32]2[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[N:35]=[CH:34][N:33]=2)[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1.C(OC([NH:49][CH2:50][CH2:51][O:52][CH:53]([CH2:57][C:58]1[CH:63]=[CH:62][C:61]([Cl:64])=[CH:60][CH:59]=1)[C:54]([OH:56])=O)=O)(C)(C)C.C(OC(=O)COCC(N)[C:73]([O:75][C:76]([CH3:79])([CH3:78])[CH3:77])=[O:74])C.ClC1C=CC(CBr)=CC=1>C(Cl)(Cl)Cl.C1COCC1>[C:73]([CH:50]([NH2:49])[CH2:51][O:52][CH:53]([CH2:57][C:58]1[CH:59]=[CH:60][C:61]([Cl:64])=[CH:62][CH:63]=1)[C:54]([N:29]1[CH2:30][CH2:31][N:26]([C:32]2[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[N:35]=[CH:34][N:33]=2)[CH2:27][CH2:28]1)=[O:56])([O:75][C:76]([CH3:79])([CH3:78])[CH3:77])=[O:74]

Participants

9

Reactant 6

HCID 682631,1'-CarbonyldiimidazoleHCID 693291-(Bromomethyl)-4-chlorobenzeneHCID 27960291-Hydroxybenzotriazole hydrateHCID 66570482HCID 66570482, compoundHCID 67540176HCID 67540176, compoundHCID 86598742HCID 86598742, compound

Product 1

HCID 67540189HCID 67540189, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranCatalystHCID 6212ChloroformSolvent

Procedure

The PS-CDI (175 mg, 0.181 mmol), HOBt monohydrate (214 mg, 0.140 mmol), 4-piperazin-1-yl-quinazoline dihydrochloride (52 mg, 0.181 mmol), and 2-(2-tert-butoxycarbonylamino-ethoxy)-3-(4-chlorophenyl)-propionic acid (48 mg, 0.140 mmol; prepared by alkylation of (2-Boc-amino-ethoxy)-acetic acid ethyl ester with 4-chlorobenzylbromide according to procedures described in the literature: Nizal S. Chandrakumar et al. J. Med. Chem. 1992, 35, 2928-2938) were suspended/dissolved in 2.5 mL of chloroform (plus 3-5 drops THF). The mixture was shaken at room temperature overnight, then treated with MP-CO3 (330 mg, 0.838 mmol) for two hours. The mixture was vacuum filtered, rinsed with chloroform, and concentrated in vacuo. The residue was purified on silica gel (1:19 DCM:EtOAc) to afford 2-(2-Boc-amino-ethoxy)-3-(4-chlorophenyl)-1-(4-quinazolin-4-yl-piperazin-1-yl)-propan-1-one. This material was dissolved in 1.0 mL of 1,4-dioxane and treated with 1.5 mL of 4M HCl in 1,4-dioxane affording slow precipitation. The mixture was sonicated briefly and stirred at room temperature overnight to completion. The resulting suspension was concentrated in vacuo, and the solids were suspended in diethyl ether, filtered under nitrogen pressure, and dried in vacuo to afford 2-(2-amino-ethoxy)-3-(4-chlorophenyl)-1-(4-quinazolin-4-yl-piperazin-1-yl)-propan-1-one dihydrochloride as a yellow powder (13 mg, 18%). LCMS (APCI+) m/z 440 [M+H]+. HPLC R2=1.75 min.

Workup

  1. filtrationfiltered
  2. washrinsed with chloroform
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified on silica gel (1:19 DCM:EtOAc)

Sources & evidence

ORD record
ord-f1e8821c600f49d5a36f6bc7510d3a3c
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

Loading…