1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (S)-N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-3-isopropyl-1,2,4-oxadiazole-5-carboxamide

HRID 1409318노트

반응식

HRID 1409318 반응식
[CH:1]([C:4]1[N:8]=[C:7]([C:9]([OH:11])=O)[O:6][N:5]=1)([CH3:3])[CH3:2].CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.[NH2:42][C@@H:43]([CH3:60])[CH2:44][N:45]1[CH:49]=[CH:48][C:47]([C:50]2[CH:57]=[C:56]([F:58])[C:53]([C:54]#[N:55])=[C:52]([Cl:59])[CH:51]=2)=[N:46]1>CN(C=O)C.O.CCOC(C)=O>[Cl:59][C:52]1[CH:51]=[C:50]([C:47]2[CH:48]=[CH:49][N:45]([CH2:44][C@@H:43]([NH:42][C:9]([C:7]3[O:6][N:5]=[C:4]([CH:1]([CH3:2])[CH3:3])[N:8]=3)=[O:11])[CH3:60])[N:46]=2)[CH:57]=[C:56]([F:58])[C:53]=1[C:54]#[N:55]

참가 물질

9

반응물 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 232010263-Isopropyl-1,2,4-oxadiazole-5-carboxylic acidHCID 67170587(S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chloro-6-fluorobenzonitrile

생성물 1

HCID 66576599(S)-N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)-3-isopropyl-1,2,4-oxadiazole-5-carboxamide수율 1.3%

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매2회HCID 8857Ethyl Acetate용매

실험 절차

3-Isopropyl-1,2,4-oxadiazole-5-carboxylic acid (1.281 mmol, 0.2 g) was dissolved in DMF (5 ml) under nitrogen atmosphere. EDCI (1.601 mmol, 0.307 g), DIPEA (3.20 mmol, 0.414 g) and HOBt (1.601 mmol, 0.216 g) were added and the resulting mixture was stirred for 20 min at RT. (S)-4-(1-(2-Aminopropyl)-1H-pyrazol-3-yl)-2-chloro-6-fluorobenzonitrile (1.067 mmol, 0.298 g) dissolved in DMF (5 ml) was added and the resulting mixture was stirred at RT for 2 days. The mixture was diluted with water and EtOAc, washed with 2 M Na2CO3, water and brine. The combined organics were dried, filtered and evaporated. The crude product was purified by preparative HPLC. 0.0056 g of the title compound was obtained. 1H-NMR (400 MHz, CDCl3): δ 1.25 (d, 3H), 1.38 (d, 6H), 3.11-3.26 (m, 1H), 4.26-4.35 (m, 1H), 4.41-4.50 (m, 1H), 4.55-4.67 (m, 1H), 6.65-6.69 (m, 1H), 7.54-7.57 (m, 1H), 7.64-7.69 (m, 1H), 7.74-7.77 (m, 1H), 8.39 (d, 1H).

후처리

  1. additionwas added
  2. stirringthe resulting mixture was stirred at RT for 2 days
  3. washwashed with 2 M Na2CO3, water and brine
  4. customThe combined organics were dried
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude product was purified by preparative HPLC

출처 및 근거

ORD 기록
ord-d1312f49bafd4715a6c1be4ec79d2ae0
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08921378B2

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