Dimethylamine → (3-Amino-5-chloro-2-cyclopropylcarbamoyl-4-methyl-thieno[2,3-b]pyridin-6-yloxy)-acetic acid dimethylamide

HRID 656646Notes

Reaction equation

HRID 656646 reaction equation
[NH2:1][C:2]1[C:10]2[C:5](=[N:6][C:7]([O:13][CH2:14][C:15]([OH:17])=O)=[C:8]([Cl:12])[C:9]=2[CH3:11])[S:4][C:3]=1[C:18](=[O:23])[NH:19][CH:20]1[CH2:22][CH2:21]1.O.ON1C2C=CC=CC=2N=N1.[CH:35]([N:38](CC)[CH:39](C)C)(C)C.Cl.CN(C)CCCN=C=NCC.CNC>CN(C=O)C.C1COCC1>[CH3:35][N:38]([CH3:39])[C:15](=[O:17])[CH2:14][O:13][C:7]1[N:6]=[C:5]2[S:4][C:3]([C:18](=[O:23])[NH:19][CH:20]3[CH2:21][CH2:22]3)=[C:2]([NH2:1])[C:10]2=[C:9]([CH3:11])[C:8]=1[Cl:12]

Participants

8

Reactant 5

HCID 674DimethylamineHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 68436813(3-Amino-5-chloro-2-cyclopropylcarbamoyl-4-methyl-thieno[2,3-b]pyridin-6-yloxy)-acetic acid

Product 1

HCID 57664395(3-Amino-5-chloro-2-cyclopropylcarbamoyl-4-methyl-thieno[2,3-b]pyridin-6-yloxy)-acetic acid dimethylamideYield 19%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (3-amino-5-chloro-2-cyclopropylcarbamoyl-4-methyl-thieno[2,3-b]pyridin-6-yloxy)-acetic acid (0.200 g, 0.562 mmol) in a 1:1 mixture of THF:DMF (1.5 ml each) are added 1-hydroxybenzotriazole hydrate (0.099 g, 0.731 mmol), N,N-diisopropylethylamine (0.109 g, 0.843 mmol), 1-[3-(dimethylamino)-propyl]-3-ethylcarbodiimide hydrochloride (0.162 g, 0.843 mmol), and dimethylamine (2.0 M in MeOH)(0.85 ml, 1.69 mmol). The resulting solution is stirred at room temperature for 24 hours, then at 50° C. for 24 hours. The reaction is cooled to room temperature and quenched by the addition of water. The mixture is partitioned between water and EtOAc (40 ml each), and the layers are shaken and separated. The aqueous layer is acidified to pH 3 with 1 N HCl and then extracted with EtOAc (40 ml). The combined organic layers are dried (anhydrous magnesium sulfate), filtered, concentrated, and flashed (100% EtOAc) to give the title compound as a white solid (0.040 g, 19%). Mass (m/z): 383.2 (M++1), 381.2 (M+−1).

Workup

  1. waitat 50° C. for 24 hours
  2. temperatureThe reaction is cooled to room temperature
  3. customquenched by the addition of water
  4. customThe mixture is partitioned between water and EtOAc (40 ml each)
  5. stirringthe layers are shaken
  6. customseparated
  7. extractionextracted with EtOAc (40 ml)
  8. dry with materialThe combined organic layers are dried (anhydrous magnesium sulfate)
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-b11e1e54d15d40bb8d6a549493fadd95
Source dataset
uspto-grants-2011_12
Patent number
US08071776B2

Reaction notes

Loading…