Ether hydrochloride → HCID 25197079, compound

HRID 2373993Notes

Reaction equation

HRID 2373993 reaction equation
C(C1C=NC=CC=1OC1C=CC(N)=CC=1F)C.FC1C=CC(CC(N=C=O)=O)=CC=1.COC1C=C[C:36]([CH2:37][NH:38][C:39]2N=CN=[C:41]([O:45][C:46]3[CH:51]=[CH:50][C:49]([NH:52][C:53]([NH:55][C:56](=[O:65])[CH2:57][C:58]4[CH:63]=[CH:62][C:61]([F:64])=[CH:60][CH:59]=4)=[O:54])=[CH:48][C:47]=3[F:66])[CH:40]=2)=[CH:35][CH:34]=1.[ClH:69].CCOCC>C(Cl)Cl.CO>[ClH:69].[CH2:35]([C:36]1[CH:37]=[N:38][CH:39]=[CH:40][C:41]=1[O:45][C:46]1[CH:51]=[CH:50][C:49]([NH:52][C:53]([NH:55][C:56](=[O:65])[CH2:57][C:58]2[CH:63]=[CH:62][C:61]([F:64])=[CH:60][CH:59]=2)=[O:54])=[CH:48][C:47]=1[F:66])[CH3:34]

Participants

7

Reactant 4

HCID 10953452Ether hydrochlorideHCID 115698931-(4-(6-(4-Methoxybenzylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-3-(2-(4-fluorophenyl)acetyl)urea2×HCID 231530882-(4-Fluorophenyl)acetyl isocyanateHCID 59852997HCID 59852997, compound

Product 1

HCID 25197079HCID 25197079, compoundYield 36%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 4-(3-ethylpyridin-4-yloxy)-3-fluorobenzenamine (23 mg, 0.10 mmol) in CH2Cl2 (1 mL) was treated with a solution of 0.3 M solution of 2-(4-fluorophenyl)acetyl isocyanate in toluene (Compound D of Example 11, 0.33 mL, 0.11 mmol) and the mixture was stirred at room temperature for 2.5 h. The mixture was concentrated under vacuum and the residue triturated with 1:1 isopropyl ether/EtOAc to give a yellow solid. The product was treated with absolute MeOH (1 mL) and 2 M HCl/Et2O (1 mL), stirred at room temperature for 5 min and concentrated under vacuum to give the title compound (15 mg, 36%) as a pale yellow solid. 1H NMR (DMSO-d6) δ 11.04 (s, 1H), 10.57 (s, 1H), 8.41 (s, 1H), 8.26 (d, 1H, J=5.6 Hz), 7.76 (dd, 1H, J=2.0, 12.7 Hz), 7.40-7.28 (m, 4H), 7.19-7.14 (m, 3H), 6.54 (d, 1H, J=5.6 Hz), 3.73 (s, 2H), 2.72 (q, 2H, J=7.6 Hz), 1.23 (t, 3H, J=7.6 Hz); MS(ESI+): m/z 412.20 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated under vacuum
  2. customthe residue triturated with 1:1 isopropyl ether/EtOAc
  3. customto give a yellow solid
  4. stirringstirred at room temperature for 5 min
  5. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-51ed7bfd9f8f4ec08fcfc25f256d9feb
Source dataset
uspto-grants-2008_12
Patent number
US07459562B2

Reaction notes

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