Hydrochloric Acid → (E)-N-(2-Amino-phenyl)-3-{4-[(2-morpholin-4-yl-ethoxy)-(4-trifluoromethyl-phenylcarbamoyl)-methyl]-phenyl}-acrylamide

HRID 1714167Notes

Reaction equation

HRID 1714167 reaction equation
C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH:14][C:15](=[O:47])/[CH:16]=[CH:17]/[C:18]1[CH:23]=[CH:22][C:21]([CH:24]([O:38][CH2:39][CH2:40][N:41]2[CH2:46][CH2:45][O:44][CH2:43][CH2:42]2)[C:25](=[O:37])[NH:26][C:27]2[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][CH:28]=2)=[CH:20][CH:19]=1)(C)(C)C.Cl>CO>[NH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH:14][C:15](=[O:47])/[CH:16]=[CH:17]/[C:18]1[CH:23]=[CH:22][C:21]([CH:24]([O:38][CH2:39][CH2:40][N:41]2[CH2:46][CH2:45][O:44][CH2:43][CH2:42]2)[C:25](=[O:37])[NH:26][C:27]2[CH:32]=[CH:31][C:30]([C:33]([F:34])([F:35])[F:36])=[CH:29][CH:28]=2)=[CH:20][CH:19]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 57820106(E)-[2-(3-{4-[(2-Morpholin-4-yl-ethoxy)-(4-trifluoromethyl-phenylcarbamoyl)-methyl]-phenyl}-acryloylamino)-phenyl]-carbamic acid tert-butyl ester

Product 1

HCID 57820043(E)-N-(2-Amino-phenyl)-3-{4-[(2-morpholin-4-yl-ethoxy)-(4-trifluoromethyl-phenylcarbamoyl)-methyl]-phenyl}-acrylamideYield 17%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(E)-[2-(3-{4-[(2-Morpholin-4-yl-ethoxy)-(4-trifluoromethyl-phenylcarbamoyl)-methyl]-phenyl}-acryloylamino)-phenyl]-carbamic acid tert-butyl ester (118 mg, 0.177 mmol) was treated with 1.25M HCl in methanol (1 mL) at room temperature for 2 hours. The reaction was quenched slowly with solid sodium bicarbonate until the pH was 6-7. The mixture was diluted in acetonitrile with a small amount of dimethylsulfoxide, passed through a 40 μm pipette filter, and then purified by preparative HPLC to obtain 17 mg desired product (17%). MS: calc'd 569 (MH+) exp 569 (MH+). 1H NMR (d6-DMSO, 400 MHz) δ 10.6 (s, 1H, rotamer a), 10.4 (s, 1H, rotamer b), 9.43 (s, 1H), 7.91 (d, 2H, J=8.0 Hz), 7.70 (d, 2H, J=8.8 Hz), 7.65 (d, 2H, J=8.0 Hz), 7.58 (d, 2H, J=8.8 Hz), 7.55 (d, 1H, J=15.6 Hz), 7.34 (d, 1H, J=6.4 Hz), 6.92 (d, 1H, J=15.6 Hz), 6.91 (t, 1H, J=6.4 Hz), 6.75 (d, 1H, J=7.4 Hz), 6.57 (t, 1H, J=7.4 Hz), 5.11 (s, 1H), 4.96 (s, 2H), 3.70 (broad m, 4H), 3.55 (broad m, 2H), 2.70-2.35 (broad m, 6H).

Workup

  1. customThe reaction was quenched slowly with solid sodium bicarbonate until the pH was 6-7
  2. additionThe mixture was diluted in acetonitrile with a small amount of dimethylsulfoxide
  3. filtrationfilter
  4. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-34b9acc20e0449ce8a23a01d658359f7
Source dataset
uspto-grants-2010_09
Patent number
US07795315B2

Reaction notes

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