4-Fluorobenzylamine → 3-Amino-5-chloro-6-[(4-fluoro-benzylcarbamoyl)-methoxy]-4-methyl-thieno[2,3-b]pyridine-2-carboxylic acid cyclopropylamide

HRID 656662Notes

Reaction equation

HRID 656662 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.C(N(CC)C(C)C)(C)C.Cl.CN(C)CCCN=C=NCC.[F:56][C:57]1[CH:64]=[CH:63][C:60]([CH2:61][NH2:62])=[CH:59][CH:58]=1>CN(C=O)C.C1COCC1>[CH:20]1([NH:19][C:18]([C:3]2[S:4][C:5]3=[N:6][C:7]([O:13][CH2:14][C:15](=[O:17])[NH:62][CH2:61][C:60]4[CH:63]=[CH:64][C:57]([F:56])=[CH:58][CH:59]=4)=[C:8]([Cl:12])[C:9]([CH3:11])=[C:10]3[C:2]=2[NH2:1])=[O:23])[CH2:22][CH2:21]1

Participants

8

Reactant 5

HCID 673264-FluorobenzylamineHCID 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 576644083-Amino-5-chloro-6-[(4-fluoro-benzylcarbamoyl)-methoxy]-4-methyl-thieno[2,3-b]pyridine-2-carboxylic acid cyclopropylamideYield 37%

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 (0.300 g, 0.843 mmol) in a 1:1 mixture of THF:DMF (2.0 ml each) are added 1-hydroxybenzotriazole hydrate (0.148 g, 1.096 mmol), N,N-diisopropylethylamine (0.163 g, 1.265 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.242 g, 1.265 mmol), and 4-fluorobenzylamine (0.317 g, 2.529 mmol). The resulting solution is stirred at room temperature for 16 hours. The reaction is quenched by the addition of water (25 ml). A yellow precipitate is formed. The mixture is cooled to 0° C. and stirred for 10 minutes, then filtered. The collected solid is slurried in 10:1 hexane:EtOAc and stirred for 10 minutes. The solid is collected by filtration and dried in the vacuum oven at 50° C. for 1 hour. This affords the title compound as a pale yellow solid (0.143 g, 37%). Mass (m/z): 463.1 (M++1), 461.1 (M+−1).

Workup

  1. customThe reaction is quenched by the addition of water (25 ml)
  2. customA yellow precipitate is formed
  3. temperatureThe mixture is cooled to 0° C.
  4. stirringstirred for 10 minutes
  5. filtrationfiltered
  6. stirringEtOAc and stirred for 10 minutes
  7. filtrationThe solid is collected by filtration
  8. customdried in the vacuum oven at 50° C. for 1 hour

Sources & evidence

ORD record
ord-d73b86e794be468aa7a19c9b857b51d9
Source dataset
uspto-grants-2011_12
Patent number
US08071776B2

Reaction notes

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