Diisopropylethylamine → HCID 69048117, compound

HRID 1867741Notes

Reaction equation

HRID 1867741 reaction equation
[Cl:1][C:2]1[C:3]([F:23])=[C:4]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH3:22])=[C:16]([CH2:19]Cl)[CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.[NH2:24][C:25]([C:27]1([NH:38][CH2:39][CH3:40])[CH2:30][N:29]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:28]1)=[O:26].C(N(C(C)C)CC)(C)C>CN(C=O)C>[NH2:24][C:25]([C:27]1([N:38]([CH2:19][C:16]2[CH:17]=[C:18]3[C:13](=[CH:14][C:15]=2[O:21][CH3:22])[N:12]=[CH:11][N:10]=[C:9]3[NH:8][C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=2[F:23])[CH2:39][CH3:40])[CH2:30][N:29]([C:31]([O:33][C:34]([CH3:35])([CH3:36])[CH3:37])=[O:32])[CH2:28]1)=[O:26]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 57979822HCID 57979822, compoundHCID 69047255HCID 69047255, compound

Product 1

HCID 69048117HCID 69048117, compoundYield 19.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-(3-Chloro-2-fluorophenyl)-6-(chloromethyl)-7-methoxyquinazolin-4-amine (360 mg, 0.93 mmol, prepared as described in Example 62) was added portionwise over 2 hours to a solution of tert-butyl 3-(aminocarbonyl)-3-(ethylamino)azetidine-1-carboxylate (294 mg, 1.21 mmol) and diisopropylethylamine (0.5 ml, 2.79 mmol) in DMF (1 ml) at 120° C. The resulting product was purified on preparative HPLC (standard basic conditions) to give tert-butyl 3-(aminocarbonyl)-3-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(ethyl)amino]azetidine-1-carboxylate as a solid (100 mg, 19%); Mass Spectrum: (M+H)+ 559. This was dissolved in 1,4-dioxan (3 ml) and a solution of concentrated hydrochloric acid (5 ml) in 1,4-dioxan (25 ml) was added dropwise. The reaction mixture was stirred overnight and concentrated under reduced pressure. The residues were triturated with a mixture of methanol/dichloromethane/diethylether to give a hydrochloride salt of 3-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(ethyl)amino]azetidine-3-carboxamide as a solid (89 mg, 100%); 1H NMR Spectrum: (CDCl3) 1.16 (t, 3H), 2.59 (q, 2H), 3.41 (d, 2H), 3.76 (d, 2H), 3.89 (s, 2H), 3.98 (s, 3H), 5.47 (brs, 1H), 7.15 (m, 2H), 7.24 (s, 1H), 7.77 (s, 1H), 7.90 (s, 1H), 8.44 (m, 1H), 8.72 (s, 1H); Mass Spectrum: (M+H)+ 459.

Workup

  1. customThe resulting product was purified on preparative HPLC (standard basic conditions)

Sources & evidence

ORD record
ord-fe4f641ecb4b482bbf284617882a144d
Source dataset
uspto-grants-2009_12
Patent number
US07632840B2

Reaction notes

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