1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (S)-4-((1-(2-(3,5-dichlorophenylamino)acetyl)piperidin-3-yl)(methyl)amino)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one

HRID 919601ノート

反応式

HRID 919601 の反応式
[CH3:1][N:2]([C@H:14]1[CH2:19][CH2:18][CH2:17][NH:16][CH2:15]1)[C:3]1[C:4]2[CH2:12][CH2:11][C:10](=[O:13])[NH:9][C:5]=2[N:6]=[CH:7][N:8]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[Cl:41][C:42]1[CH:43]=[C:44]([NH:49][CH2:50][C:51](O)=[O:52])[CH:45]=[C:46]([Cl:48])[CH:47]=1.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[Cl:41][C:42]1[CH:43]=[C:44]([NH:49][CH2:50][C:51]([N:16]2[CH2:17][CH2:18][CH2:19][C@H:14]([N:2]([CH3:1])[C:3]3[C:4]4[CH2:12][CH2:11][C:10](=[O:13])[NH:9][C:5]=4[N:6]=[CH:7][N:8]=3)[CH2:15]2)=[O:52])[CH:45]=[C:46]([Cl:48])[CH:47]=1

参加物

8

反応物 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 13138167(3,5-Dichlorophenyl)glycineHCID 86706466(S)-4-(methyl(piperidin-3-yl)amino)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one

生成物 1

HCID 56971630(S)-4-((1-(2-(3,5-dichlorophenylamino)acetyl)piperidin-3-yl)(methyl)amino)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one収率 9,465.6%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of (S)-4-(methyl(piperidin-3-yl)amino)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one (150 mg, 0.6 mmol) in DMF (5 mL) was added EDCI (164 mg, 0.85 mmol), HOBt (114 mg, 0.85 mmol), 2-(3,5-dichlorophenylamino)acetic acid (126 mg, 0.57 mmol) and DIEA (147 mg, 1.14 mmol) at 0° C. The reaction mixture was stirred at rt overnight, diluted with EtOAc and washed with water. The aqueous layer was extracted with the EtOAc, the combined organic layer was dried over Na2SO4 and evaporated in vacuo to give the crude compound that was purified by column chromatography (silica gel, gradient MeOH in CH2Cl2) to afford (25 g, 9%) of the titled compound. 1H NMR (400 MHz, CD3OD): δ 8.29 (s, 1H), 6.61-6.60 (d, 1H), 6.59-6.58 (m, 2H), 4.28-4.01 (m, 1H), 3.99-3.95 (m, 2H), 3.68-3.66 (t, J=4.4 Hz, 1H), 3.57-3.54 (t, J=4.4 Hz, 1H), 3.34 (s, 3H), 3.08-2.97 (m, 3H), 2.60-2.53 (m, 2H), 2.03-2.00 (m, 2H), 1.43-1.26 (m, 3H). LC-MS: m/z [M+1]=463.

後処理

  1. washwashed with water
  2. extractionThe aqueous layer was extracted with the EtOAc
  3. dry with materialthe combined organic layer was dried over Na2SO4
  4. customevaporated in vacuo
  5. customto give the crude compound that
  6. customwas purified by column chromatography (silica gel, gradient MeOH in CH2Cl2)

出典と根拠

ORDレコード
ord-ff2fd29f2d674bf09eec79c1c9865a84
出典データセット
uspto-grants-2016_03
特許番号
US09273028B2

反応ノート

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