Diisopropylethylamine → 3-Amino-5-chloro-4-methyl-6-[(2-morpholin-4-yl-ethylcarbamoyl)-methoxy]-thieno[2,3-b]pyridine-2-carboxylic acid cyclopropylamide

HRID 656663Notes

Reaction equation

HRID 656663 reaction equation
[NH2:1][C:2]1[C:10]2[C:5](=[N:6][C:7]([O:13][CH2:14][C:15](O)=[O:16])=[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.[NH2:56][CH2:57][CH2:58][N:59]1[CH2:64][CH2:63][O:62][CH2:61][CH2:60]1>CCCCCC.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:16])[NH:56][CH2:57][CH2:58][N:59]4[CH2:64][CH2:63][O:62][CH2:61][CH2:60]4)=[C:8]([Cl:12])[C:9]([CH3:11])=[C:10]3[C:2]=2[NH2:1])=[O:23])[CH2:21][CH2:22]1

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 4082852-MorpholinoethylamineHCID 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 576643963-Amino-5-chloro-4-methyl-6-[(2-morpholin-4-yl-ethylcarbamoyl)-methoxy]-thieno[2,3-b]pyridine-2-carboxylic acid cyclopropylamideYield 13.4%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

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-(2-aminoethyl)morpholine (0.329 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). If no precipitate forms, the mixture may be acidified to pH2 with 1 N HCl and extracted with EtOAc (25 ml). The organic layer is discarded and the aqueous layer is made basic (pH12) with 5N NaOH and extracted with EtOAc (40 ml). The organic layer is dried (anhydrous magnesium sulfate), filtered, and concentrated to give a yellow solid. The solid is slurried in 3:1 hexane:EtOAc (10 ml), then filtered. The collected solid is dried in the vacuum oven at 50° C. for 72 hours. This affords the title compound as a yellow solid (0.053 g, 13%). Mass (m/z): 468.2 (M++1), 466.2 (M+−1).

Workup

  1. customThe reaction is quenched by the addition of water (25 ml)
  2. extractionextracted with EtOAc (25 ml)
  3. extractionextracted with EtOAc (40 ml)
  4. dry with materialThe organic layer is dried (anhydrous magnesium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a yellow solid
  8. filtrationEtOAc (10 ml), then filtered
  9. customThe collected solid is dried in the vacuum oven at 50° C. for 72 hours

Sources & evidence

ORD record
ord-06dad862ab1940be8ca613fde15fb128
Source dataset
uspto-grants-2011_12
Patent number
US08071776B2

Reaction notes

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