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

HRID 1256381노트

반응식

HRID 1256381 반응식
[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

참가 물질

8

반응물 4

HCID 962WaterHCID 65578Oxalyl chloride2회HCID 582071812-Methyl-7-phenylpyrazolo[1,5-a]pyrimidin-5-amineHCID 588411094-(1-(Methoxycarbonyl)cyclopropyl)benzoic acid

생성물 1

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

시약·촉매·용매 3

HCID 6228Dimethylformamide촉매HCID 1049Pyridine용매HCID 6344Dichloromethane용매

실험 절차

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, 1 H), 8.08-8.04 (m, 2 H), 8.04-7.99 (m, 2 H), 7.96 (s, 1 H), 7.66-7.60 (m, 3 H), 7.52-7.48 (m, 2 H), 6.40 (s, 1 H), 3.57 (s, 3 H), 2.40 (s, 3 H), 1.56-1.50 (m, 2 H), 1.31-1.25 (m, 2 H); ESI-MS: m/z 427.4 (M+H)+.

후처리

  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)

출처 및 근거

ORD 기록
ord-33357c42bc2b46ca91c8103fd40bc0a7
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08461163B2

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