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 1409318ノート

反応式

HRID 1409318 の反応式
[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]

参加物

9

反応物 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

生成物 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-carboxamide収率 1.3%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-d1312f49bafd4715a6c1be4ec79d2ae0
出典データセット
uspto-grants-2014_12
特許番号
US08921378B2

反応ノート

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