4-Methylmorpholine → HCID 16718838, compound

HRID 1916349Notes

Reaction equation

HRID 1916349 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:16][C:15]3[C:14](=[O:17])[N:13]([C:18]4[CH:28]=[CH:27][C:21]([O:22][CH2:23][C:24]([OH:26])=O)=[C:20]([O:29][CH3:30])[CH:19]=4)[CH:12]=[N:11][C:10]=3[CH:9]=2)=[CH:4][CH:3]=1.[NH:31]1[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1.CCN=C=NCCCN(C)C.Cl.O.OC1C2N=NNC=2C=CC=1.CN1CCOCC1>CN(C=O)C.C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[S:16][C:15]3[C:14](=[O:17])[N:13]([C:18]4[CH:28]=[CH:27][C:21]([O:22][CH2:23][C:24](=[O:26])[N:31]5[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]5)=[C:20]([O:29][CH3:30])[CH:19]=4)[CH:12]=[N:11][C:10]=3[CH:9]=2)=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 8082PiperidineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 16718835HCID 16718835, compoundHCID 178526939HCID 178526939, compound

Product 1

HCID 16718838HCID 16718838, compoundYield 87%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 2-(4-(6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3(4H)-yl)-2-methoxyphenoxy)acetic acid Example 15 (20 mg; 0.045 mmol), piperidine (7 uL; 0.068 mmol), EDC hydrochloride (10 mg; 0.054 mmol) and hydroxybenzotriazole hydrate (8 mg; 0.054 mmol) in 70 uL of DMF and 415 uL of CH2Cl2 was cooled to 0° C. After addition of N-methylmorpholine (6 uL; 0.054 mmol), the solution allowed to warm to rt and stir for 23 h. Following concentration under reduced pressure and dilution with water, the mixture was extracted with EtOAc. The organic layer was washed with water and brine, dried over MgSO4, filtered and the filtrate concentrated under reduced pressure. The residue was triturated in MeOH to afford the title compound (20 mg; 87%) as a white solid. 1H NMR (CDCl3) δ 1.57-1.67 (m, 6H), 3.52-3.59 (m, 4H), 3.90 (s, 3H), 4.81 (s, 2H), 6.91 (dd, J=8.25 Hz, 2.20 Hz, 1H), 6.98 (d, J=2.75 Hz, 1H), 7.09 (d, J=8.25 Hz, 1H), 7.44 (d, J=8.79 Hz, 2H), 7.53 (s, 1H), 7.66 (d, J=8.80 Hz, 2H), 8.13 (s, 1H); 13C NMR (CDCl3) δ 24.42, 25.54, 26.47, 43.27, 46.39, 56.15, 68.65, 111.13, 113.98, 119.14, 120.86, 123.21, 127.65, 129.45, 130.75, 131.54, 135.68, 148.14, 148.28, 149.88, 151.66, 156.75, 157.40, 165.65; HPLC (Method #1): 3.65 min retention time; MS (ES): m/z 510 [M+H]+.

Workup

  1. concentrationconcentration under reduced pressure and dilution with water
  2. extractionthe mixture was extracted with EtOAc
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated under reduced pressure
  7. customThe residue was triturated in MeOH

Sources & evidence

ORD record
ord-a99a1cbc15b44122b4486ab14f64def2
Source dataset
uspto-grants-2013_12
Patent number
US08618115B2

Reaction notes

Loading…