1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 6-Pyrazol-1-yl-imidazo[1,2-a]pyridine-2-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide

HRID 1093876노트

반응식

HRID 1093876 반응식
CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[N:31]1([C:36]2[CH:37]=[CH:38][C:39]3[N:40]([CH:42]=[C:43]([C:45]([OH:47])=O)[N:44]=3)[CH:41]=2)[CH:35]=[CH:34][CH:33]=[N:32]1.Cl.[NH2:49][CH2:50][C:51]([N:53]1[CH2:58][CH2:57][CH:56]([O:59][C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][C:61]=2[Cl:66])[CH2:55][CH2:54]1)=[O:52]>CN(C=O)C.O>[Cl:66][C:61]1[CH:62]=[CH:63][CH:64]=[CH:65][C:60]=1[O:59][CH:56]1[CH2:55][CH2:54][N:53]([C:51](=[O:52])[CH2:50][NH:49][C:45]([C:43]2[N:44]=[C:39]3[CH:38]=[CH:37][C:36]([N:31]4[CH:35]=[CH:34][CH:33]=[N:32]4)=[CH:41][N:40]3[CH:42]=2)=[O:47])[CH2:58][CH2:57]1

참가 물질

8

반응물 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 578744966-Pyrazol-1-yl-imidazo[1,2-a]pyridine-2-carboxylic acidHCID 665915282-Amino-1-[4-(2-chloro-phenoxy)-piperidin-1-yl]-ethanone hydrochloride

생성물 1

HCID 578745136-Pyrazol-1-yl-imidazo[1,2-a]pyridine-2-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide수율 36.1%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

DIPEA (169 mg, 1.3 mmol) followed by HOBt (39 mg, 0.29 mmol) and EDCI (75 mg, 0.39 mmol) was added to a stirred solution of 6-pyrazol-1-yl-imidazo[1,2-a]pyridine-2-carboxylic acid (60 mg, 0.26 mmol) in DMF (1 mL). After 2 minutes of stirring, 2-amino-1-[4-(2-chloro-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (80 mg, 0.26 mmol) (prepared according to Step 1 and 5 of the General Scheme) was added and the resulting mixture was stirred at room temperature overnight. Cold water was added and the reaction mixture was partitioned with ethyl acetate, the organic layer was dried over sodium sulfate and concentrated under reduced pressure. Purification by preparative HPLC afforded 45 mg (33% Yield) of 6-pyrazol-1-yl-imidazo[1,2-a]pyridine-2-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 479, 97.25%. 1H NMR (300 MHz, DMSO-d6): δ 9.2 (s, 1H), 8.5 (m, 2H), 8.4 (t, 1H), 8.0 (dd, 1H), 7.8 (m, 2H), 7.4 (dd, 1H), 7.53 (m, 2H), 7.0 (m, 1H), 6.6 (t, 1H), 4.8 (m, 1H), 4.0 (bs, 1H), 4.2 (d, 2H), 3.7 (m, 2H), 3.4 (m, 2H), 2.0 (m, 2H), 1.7 (m, 2H).

후처리

  1. additionwas added
  2. stirringthe resulting mixture was stirred at room temperature overnight
  3. customthe reaction mixture was partitioned with ethyl acetate
  4. dry with materialthe organic layer was dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customPurification by preparative HPLC

출처 및 근거

ORD 기록
ord-bdb4d2435036427f96034b2b823f66e9
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08129376B2

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