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 919601노트

반응식

HRID 919601 반응식
[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

참가 물질

8

반응물 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

생성물 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)-one수율 9,465.6%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-ff2fd29f2d674bf09eec79c1c9865a84
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09273028B2

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