1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (R)-2-(3,5-dichlorophenylamino)-1-(3-(methyl(1H-pyrazolo[3,4-d]pyrimidin-4-yl)amino)piperidin-1-yl)ethanone

HRID 919568노트

반응식

HRID 919568 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][CH2:10][C:11]([OH:13])=O)[CH:5]=[C:6]([Cl:8])[CH:7]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[CH3:35][N:36]([C@@H:46]1[CH2:51][CH2:50][CH2:49][NH:48][CH2:47]1)[C:37]1[N:42]=[CH:41][N:40]=[C:39]2[NH:43][N:44]=[CH:45][C:38]=12.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[Cl:8][C:6]1[CH:5]=[C:4]([NH:9][CH2:10][C:11]([N:48]2[CH2:49][CH2:50][CH2:51][C@@H:46]([N:36]([CH3:35])[C:37]3[N:42]=[CH:41][N:40]=[C:39]4[NH:43][N:44]=[CH:45][C:38]=34)[CH2:47]2)=[O:13])[CH:3]=[C:2]([Cl:1])[CH:7]=1

참가 물질

8

반응물 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 13138167(3,5-Dichlorophenyl)glycineHCID 86706447(R)-N-methyl-N-(piperidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

생성물 1

HCID 86706448(R)-2-(3,5-dichlorophenylamino)-1-(3-(methyl(1H-pyrazolo[3,4-d]pyrimidin-4-yl)amino)piperidin-1-yl)ethanone수율 15%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 2-(3,5-dichlorophenylamino)acetic acid (170 mg, 0.77 mmol) in DMF (5 mL) was added HOBt (156 mg, 1.16 mmol) at 0° C. and the reaction mixture was stirred for 10 min, followed by the addition of EDCI (222 mg, 1.16 mmol), (R)—N-methyl-N-(piperidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (180 mg, 0.77 mmol) and DIEA (150 mg, 1.16 mmol). The reaction mixture was allowed to warm to rt and was stirred overnight, diluted with EtOAc (50 mL) and washed with water (3×20 mL). The EtOAc layer was dried over Na2SO4 and evaporated in vacuo to give a residue that purified by column chromatography (silica gel, gradient MeOH in DCM) to afford the titled intermediate (50 mg, 14.8%). 1H NMR (400 MHz, DMSO-d6): δ 13.50 (d, J=10.8 Hz, 1H), 8.22 (s, 1H), 8.17 (m, 1H), 6.77 (s, 1H), 6.70 (s, 1H), 6.62 (s, 1H), 6.32 (m, 1H), 4.40 (d, J=12.4 Hz, 1H), 4.00 (m, 3H), 3.28 (s, 3H), 3.02 (t, J=7.8 Hz, 1H), 2.80 (m, 1H), 2.62 (t, J=7.8 Hz, 1H), 2.00 (m, 2H), 1.82 (m, 2H). LC-MS: m/z [M+1]=434.

후처리

  1. stirringwas stirred overnight
  2. washwashed with water (3×20 mL)
  3. dry with materialThe EtOAc layer was dried over Na2SO4
  4. customevaporated in vacuo
  5. customto give a residue
  6. customthat purified by column chromatography (silica gel, gradient MeOH in DCM)

출처 및 근거

ORD 기록
ord-a1fe99586ffb4b0c9012bd5bff6bc2cd
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09273028B2

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