Diisopropylethylamine → 4-Piperidin-1-yl-but-2-enoic acid [4-(3-chloro-4-fluoro-phenylamino)-7-(3-morpholin-4-yl-propoxy)-quinazolin-6-yl]-amide

HRID 1258445Notes

Reaction equation

HRID 1258445 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:21][CH2:22][CH2:23][CH2:24][N:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8].CCN(C(C)C)C(C)C.[N:40]1([CH2:46][CH:47]=[CH:48][C:49](Cl)=[O:50])[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]1>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:21][CH2:22][CH2:23][CH2:24][N:25]4[CH2:26][CH2:27][O:28][CH2:29][CH2:30]4)=[C:17]([NH:20][C:49](=[O:50])[CH:48]=[CH:47][CH2:46][N:40]4[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]4)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 10137640N4-(3-Chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)quinazoline-4,6-diamineHCID 72280550HCID 72280550, compound

Product 1

HCID 730729914-Piperidin-1-yl-but-2-enoic acid [4-(3-chloro-4-fluoro-phenylamino)-7-(3-morpholin-4-yl-propoxy)-quinazolin-6-yl]-amideYield 2.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

N*4*-(3-Chloro-4-fluoro-phenyl)-7-(3-morpholin-4-yl-propoxy)-quinazoline-4,6-diamine (510 mg, 1.18 mmol) and DIPEA (620 μL, 3.55 mmol) were combined in tetrahydrofuran (10 mL) and cooled to 0° C. 4-Piperidin-1-yl-but-2-enoyl chloride (278 mg, 1.48 mmol) was added and the reaction stirred at 0° C. for 2 hours. The mixture was quenched with ethyl acetate, dried with MgSO4 and concentrated. The residue was purified using chromatography on silica eluting with 15%-20% MeOH in CH2Cl2 to yield the desired product (20 mg). 400 MHz 1H NMR (DMSO-d6) δ 8.82 (s, 1H), 8.50 (s, 1H), 8.11 (dd, 1H, J=6.9, 2.6 Hz), 7.77 (m, 1H), 7.40 (t, 1H, J=9.0 Hz), 7.25 (s, 1H), 6.76 (m, 1H), 6.53 (m, 1H), 4.23 (t, 2H, J=6.0 Hz), 3.55 (m, 4H), 3.08 (m, 2H), 2.40 (m, 10H), 1.96 (m, 2H), 1.29 (m, 6H). MS m/z 584 (M+1).

Workup

  1. customThe mixture was quenched with ethyl acetate
  2. dry with materialdried with MgSO4
  3. concentrationconcentrated
  4. customThe residue was purified

Sources & evidence

ORD record
ord-0ad7be1b42634cf68c93cd8b374620d7
Source dataset
uspto-grants-2013_06
Patent number
US08466165B2

Reaction notes

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