Diisopropylethylamine → (1-methyl-1H-pyrrol-2-yl)-[3-(2-chloro-6,7-dihydrothieno[3,2-d]pyrimidin-4-ylamino)piperidin-1-yl]methanone

HRID 1788022ノート

反応式

HRID 1788022 の反応式
C1(N2CCN([C:13]3[N:14]=[C:15]([NH:22][C@H:23]4[CH2:27][CH2:26][CH2:25][C@@H:24]4[NH:28][C:29](=[O:35])OC(C)(C)C)[C:16]4[S:21][CH2:20][CH2:19][C:17]=4[N:18]=3)CC2)C=CC=CC=1.[CH:36]([N:39]([CH:42]([CH3:44])C)[CH2:40]C)([CH3:38])C.Cl.[Cl:46]C1N=C(NC2CCCNC2)C2SCCC=2N=1>CS(C)=O>[CH3:40][N:39]1[CH:36]=[CH:38][CH:44]=[C:42]1[C:29]([N:28]1[CH2:25][CH2:26][CH2:27][CH:23]([NH:22][C:15]2[C:16]3[S:21][CH2:20][CH2:19][C:17]=3[N:18]=[C:13]([Cl:46])[N:14]=2)[CH2:24]1)=[O:35]

参加物

5

反応物 3

HCID 81531Diisopropylethylamine2 回HCID 86616269tert-butyl {(1S,2S)-2-[2-(4-phenylpiperazin-1-yl)-6,7-dihydrothieno[3,2-d]pyrimidin-4-ylamino]cyclopentyl}carbamateHCID 86616275(2-Chloro-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)piperidin-3-ylamine hydrochloride

生成物 1

HCID 86616276(1-methyl-1H-pyrrol-2-yl)-[3-(2-chloro-6,7-dihydrothieno[3,2-d]pyrimidin-4-ylamino)piperidin-1-yl]methanone収率 85.6%

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

実験手順

0.462 g (3.7 mmol) of 1-methyl-1H-pyrrol-2-carboxylic acid (VII), 1.4 g (9.7 mmol) of O-(7-azabenzotriazol-1-yl-)-N,N,N′,N′-tetramethyluroniumhexafluorophosphate (HATU), and 0.640 mL (3.7 mmol) of diisopropylethylamine are placed in 10 mL of dimethylsulfoxide, then stirred for 0.1 hours at ambient temperature. 0.814 g (3.0 mmol) of (2-chloro-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)piperidin-3-ylamine hydrochloride (VI) and 3.7 mmol of diisopropylethylamine are added, then the mixture is stirred for 16 hours at ambient temperature. Then the reaction mixture is suction filtered through Alox, and the mother liquor is concentrated by evaporation. The residue is combined with 1 N sodium hydroxide solution and extracted with dichloromethane. The organic phase is separated off using a phase separator and evaporated to dryness. The crude product is purified by chromatography through a Biotage silica gel cartridge 40 s with petroleum ether/ethyl acetate 1:1. 0.970 g of product VIII (85%) is obtained.

後処理

  1. stirringthe mixture is stirred for 16 hours at ambient temperature
  2. filtrationfiltered through Alox
  3. concentrationthe mother liquor is concentrated by evaporation
  4. extractionextracted with dichloromethane
  5. customThe organic phase is separated off
  6. customevaporated to dryness
  7. customThe crude product is purified by chromatography through a Biotage silica gel cartridge 40 s with petroleum ether/ethyl acetate 1:1

出典と根拠

ORDレコード
ord-07797c4aee8a46c3a2a3c4088338977c
出典データセット
uspto-grants-2009_03
特許番号
US07511045B2

反応ノート

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