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

HRID 656663ノート

反応式

HRID 656663 の反応式
[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

参加物

9

反応物 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

生成物 1

HCID 576643963-Amino-5-chloro-4-methyl-6-[(2-morpholin-4-yl-ethylcarbamoyl)-methoxy]-thieno[2,3-b]pyridine-2-carboxylic acid cyclopropylamide収率 13.4%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒HCID 8058Hexane溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-06dad862ab1940be8ca613fde15fb128
出典データセット
uspto-grants-2011_12
特許番号
US08071776B2

反応ノート

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