Water → Methyl 1-(4-(2-methyl-7-phenylpyrazolo[1,5-a]pyrimidin-5-ylcarbamoyl)phenyl)cyclopropanecarboxylate

HRID 1409222ノート

反応式

HRID 1409222 の反応式
[CH3:1][O:2][C:3]([C:5]1([C:8]2[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][CH:9]=2)[CH2:7][CH2:6]1)=[O:4].C(Cl)(=O)C(Cl)=O.[CH3:23][C:24]1[CH:39]=[C:27]2[N:28]=[C:29]([NH2:38])[CH:30]=[C:31]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[N:26]2[N:25]=1.O>C(Cl)Cl.CN(C=O)C.N1C=CC=CC=1>[CH3:23][C:24]1[CH:39]=[C:27]2[N:28]=[C:29]([NH:38][C:12]([C:11]3[CH:10]=[CH:9][C:8]([C:5]4([C:3]([O:2][CH3:1])=[O:4])[CH2:6][CH2:7]4)=[CH:16][CH:15]=3)=[O:14])[CH:30]=[C:31]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[N:26]2[N:25]=1

参加物

8

反応物 4

HCID 962WaterHCID 65578Oxalyl chloride2 回HCID 582071812-Methyl-7-phenylpyrazolo[1,5-a]pyrimidin-5-amineHCID 588411094-(1-(Methoxycarbonyl)cyclopropyl)benzoic acid

生成物 1

HCID 67064610Methyl 1-(4-(2-methyl-7-phenylpyrazolo[1,5-a]pyrimidin-5-ylcarbamoyl)phenyl)cyclopropanecarboxylate収率 24.7%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide触媒HCID 1049Pyridine溶媒HCID 6344Dichloromethane溶媒

実験手順

4-(1-(Methoxycarbonyl)cyclopropyl)benzoic acid (200 mg, 0.91 mmol) was suspended in CH2Cl2 (5 ml). At 0° C., oxalyl chloride (0.50 ml, 1.0 mmol) was then added, followed by 2 drops of DMF. The mixture was warmed to room temperature. After 2 hours, an additional amount of oxalyl chloride (0.15 ml) was added. After the reaction was completed, 2-methyl-7-phenylpyrazolo[1,5-a]pyrimidin-5-amine (10A, 200 mg, 0.91 mmol) in pyridine (5 ml) was added. After the reaction was complete, water was added and the volatiles were removed in vacuo. The aqueous residue was extracted with EtOAc 3 times. The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo. The crude product was purified by preparatory HPLC (65-80% MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a yellow powder (96 mg, 24% yield). 1H NMR (400 MHz, DMSO-d6) δ=11.27 (s, 1H), 8.08-8.04 (m, 2H), 8.04-7.99 (m, 2H), 7.96 (s, 1H), 7.66-7.60 (m, 3H), 7.52-7.48 (m, 2H), 6.40 (s, 1H), 3.57 (s, 3H), 2.40 (s, 3H), 1.56-1.50 (m, 2H), 1.31-1.25 (m, 2H); ESI-MS: m/z 427.4 (M+H)+.

後処理

  1. customthe volatiles were removed in vacuo
  2. extractionThe aqueous residue was extracted with EtOAc 3 times
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by preparatory HPLC (65-80% MeCN/H2O gradient+0.01% TFA)

出典と根拠

ORDレコード
ord-2ef82258262644a88d2660ce48290fc5
出典データセット
uspto-grants-2014_12
特許番号
US08921358B2

反応ノート

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