Ammonia → HCID 11237777, compound

HRID 1864222Notes

Reaction equation

HRID 1864222 reaction equation
ClC1C=[C:4]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][C:25]=3[O:27][CH2:28][CH2:29][NH:30][CH2:31][CH2:32][OH:33])[N:20]=[CH:19][N:18]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1.C([O:37][CH2:38][C:39](Cl)=[O:40])(=O)C.[CH3:42]CN(C(C)C)C(C)C.N.[CH2:52]([Cl:54])Cl>CO>[Cl:54][C:52]1[CH:42]=[C:4]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][C:25]=3[O:27][CH2:28][CH2:29][N:30]([CH2:31][CH2:32][OH:33])[C:38](=[O:37])[CH2:39][OH:40])[N:20]=[CH:19][N:18]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1

Participants

7

Reactant 5

HCID 222AmmoniaHCID 6344DichloromethaneHCID 26297Acetoxyacetyl chlorideHCID 81531DiisopropylethylamineHCID 69055369HCID 69055369, compound

Product 1

HCID 11237777HCID 11237777, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

2-({2-[(4-{[3-Chloro-4-(pyridin-2-ylmethoxy)phenyl]amino}quinazolin-5-yl)oxy]ethyl}amino)ethanol (obtained as described in Example 22, preparation of starting materials) (0.208 g) in DCM (10 ml) was treated with 2-chloro-2-oxoethyl acetate (0.091 g) and DIPEA (0.173 g) and stirred for 30 minutes. 7N Ammonia in methanol (20 ml) was added and the solution stirred overnight. The mixture was evaporated and purified by chromatography using DCM to 8% 7N ammonia in methanol in DCM to give the title compound in 30% yield; NMR spectrum (DMSO-d6) 3.37 (t, 2H), 3.56 (t, 2H), 3.95 (t, 2H), 4.11-4.17 (m, 2H), 4.25 (t, 1H), 4.44 (t, 2H), 4.91 (t, 1H), 5.31 (s, 2H), 7.17 (d, 1H), 7.25 (d, 1H), 7.32-7.40 (m, 2H), 7.59 (d, 2H), 7.70-7.76 (m, 1H), 7.86-7.91 (m, 1H), 8.00 (d, 1H), 8.46 (s, 1H), 8.61 (d, 1H), 9.85 (s, 1H); Mass spectrum MH+ 524.

Workup

  1. stirringthe solution stirred overnight
  2. customThe mixture was evaporated
  3. custompurified by chromatography

Sources & evidence

ORD record
ord-7780426457b244a0b663930e431f1bd0
Source dataset
uspto-grants-2009_12
Patent number
US07625908B2

Reaction notes

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