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

HRID 1788022노트

반응식

HRID 1788022 반응식
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]

참가 물질

5

반응물 3

HCID 81531Diisopropylethylamine2회HCID 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

생성물 1

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

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-07797c4aee8a46c3a2a3c4088338977c
출처 데이터셋
uspto-grants-2009_03
특허 번호
US07511045B2

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