Diisopropylethylamine → HCID 66762641, compound

HRID 578656Notes

Reaction equation

HRID 578656 reaction equation
Cl[C:2]1[C:11]2[C:6](=[C:7]([C:13]([O:15][CH3:16])=[O:14])[CH:8]=[C:9]([Cl:12])[CH:10]=2)[N:5]=[CH:4][N:3]=1.C(N(C(C)C)C(C)C)C.[NH2:26][CH:27]([C:29]1[CH:30]=[C:31]([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[CH:32]=[CH:33][CH:34]=1)[CH3:28]>>[CH3:16][O:15][C:13]([C:7]1[CH:8]=[C:9]([Cl:12])[CH:10]=[C:11]2[C:6]=1[N:5]=[CH:4][N:3]=[C:2]2[NH:26][CH:27]([C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([NH:35][C:36]([O:37][C:38]([CH3:39])([CH3:41])[CH3:40])=[O:42])[CH:30]=1)[CH3:28])=[O:14]

Participants

4

Reactant 3

HCID 81531DiisopropylethylamineHCID 16740731tert-Butyl [3-(1-aminoethyl)phenyl]carbamateHCID 77231308HCID 77231308, compound

Product 1

HCID 66762641HCID 66762641, compound

Procedure

To a solution of methyl 4,6-dichloroquinazoline-8-carboxylate (574 mg; 2.23 mmol; 1.00 eq.) in acetonenitrile (5 ml) containing N-ethyl-N-isopropylpropan-2-amine (0.80 ml; 4.47 mmol; 2.00 eq.) was added tert-butyl [3-(1-aminoethyl)phenyl]carbamate (543 mg; 2.30 mmol; 1.03 eq.), the reaction mixture was stirred at RT overnight. Concentrated to get 4-[1-(3-tert-butoxycarbonylamino-phenyl)-ethylamino]-6-chloro-quinazoline-8-carboxylic acid methyl ester. To this crude was added methanolic ammonia (3.19 ml; 7.00 M; 22.33 mmol; 10.00 eq.) and stirred at RT for 48 h. The solvent was removed and the residue, {3-[1-(8-Carbamoyl-6-chloro-quinazolin-4-ylamino)-ethyl]-phenyl}-carbamic acid tert-butyl ester was treated with 4.0M hydrogen chloride in dioxane (5.58 ml; 4.00 M; 22.33 mmol; 10.00 eq.) and methanol (6.45 ml). Stirred overnight, concentrated and purified by HPLC to collect the title product (130 mg) in 14% over all yield. MS (M+1) 342.

Workup

  1. concentrationConcentrated

Sources & evidence

ORD record
ord-2050b01abb804facaa747d7394a91e12
Source dataset
uspto-grants-2015_05
Patent number
US09040560B2

Reaction notes

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