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 919568ノート

反応式

HRID 919568 の反応式
[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

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-a1fe99586ffb4b0c9012bd5bff6bc2cd
出典データセット
uspto-grants-2016_03
特許番号
US09273028B2

反応ノート

読み込み中…