Citric Acid → HCID 178481813、化合物

HRID 1713754ノート

反応式

HRID 1713754 の反応式
[C:1]([C:8]1[NH:9]C=CN=1)([C:3]1[NH:4][CH:5]=[CH:6][N:7]=1)=S.NC1N(C)N=CC=1.[NH:20]([C:22](=[O:43])[C:23]([NH:25][C:26]1[CH:31]=[CH:30][C:29]([C@H:32]2[CH2:37][CH2:36][C@H:35]([CH2:38][C:39]([O:41]C)=[O:40])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1)=[O:24])[NH2:21].CCN=C=NCCCN(C)C.[OH-].[Li+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CC(N(C)C)=O.C1COCC1.O.CO>[CH3:5][N:4]1[C:3]([NH:7][C:6]2[O:43][C:22]([C:23]([NH:25][C:26]3[CH:31]=[CH:30][C:29]([C@H:32]4[CH2:37][CH2:36][C@H:35]([CH2:38][C:39]([OH:41])=[O:40])[CH2:34][CH2:33]4)=[CH:28][CH:27]=3)=[O:24])=[N:20][N:21]=2)=[CH:1][CH:8]=[N:9]1

参加物

11

反応物 6

HCID 311Citric AcidHCID 3939Lithium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 1369272-Methyl-2H-pyrazol-3-ylamineHCID 11412697Thiocarbonyl diimidazoleHCID 178500682HCID 178500682、化合物2 回

生成物 1

HCID 178481813HCID 178481813、化合物収率 26%

試薬・触媒・溶媒 4

HCID 887Methanol溶媒HCID 962Water溶媒2 回HCID 8028Tetrahydrofuran溶媒HCID 31374Dimethylacetamide溶媒

実験手順

Thiocarbonyl diimidazole (179 mg, 1.00 mmol) was added in one portion to a solution of 5-amino-1-methylpyrazole (98 mg, 1.00 mmol) in DMA (5 mL) and the solution was stirred at room temperature for 6 h. Methyl [trans-4-(4-{[hydrazino(oxo)acetyl]amino}phenyl)-cyclohexyl]acetate (Intermediate 43, 267 mg, 0.80 mmol) was added in one portion and the reaction mixture was stirred at room temperature for 20 h and then heated at 80° C. for 10 minutes in the microwave. The solution was cooled to room temperature and EDCI (192 mg, 1.00 mmol) was added in one portion and the reaction mixture was heated to 90° C. for 15 minutes in the microwave. The reaction mixture was cooled to room temperature and poured into water (200 mL). The mixture was concentrated in vacuo to leave a gum, which was recrystallised (CH3CN) to leave a gummy solid. Filtration followed by concentration in vacuo of the filtrate gave the crude oxadiazole methyl ester intermediate that was used with no further purification; MS m/e MH+ 439. Lithium hydroxide (420 mg, 10.0 mmol) was added in one portion to a solution of the crude oxadiazole methyl ester intermediate in a mixture of THF (4 mL), MeOH (8 mL) and water (4 mL) and the reaction mixture was stirred at 35° C. for 4 h. Citric acid (30 mL) was added and the mixture was filtered to leave a solid that was recrystallised (MeOH) to give the title compound (87 mg, 26%) as a solid; 1H NMR δ 1.07-1.17 (2H, m), 1.41-1.51 (2H, m), 1.70-1.84 (5H, m), 2.14-2.16 (2H, d), 3.75 (3H, s), 6.70 (1H, s), 7.21-7.24 (2H, m), 7.40 (1H, s), 7.67-7.74 (2H, m); MS m/e MH+ 425.

後処理

  1. stirringthe reaction mixture was stirred at room temperature for 20 h
  2. temperatureheated at 80° C. for 10 minutes in the microwave
  3. temperatureThe solution was cooled to room temperature
  4. temperaturethe reaction mixture was heated to 90° C. for 15 minutes in the microwave
  5. temperatureThe reaction mixture was cooled to room temperature
  6. concentrationThe mixture was concentrated in vacuo
  7. customto leave a gum, which
  8. customwas recrystallised (CH3CN)
  9. customto leave a gummy solid
  10. filtrationFiltration
  11. concentrationfollowed by concentration in vacuo of the filtrate
  12. customgave the crude oxadiazole methyl ester intermediate that
  13. customwas used with no further purification
  14. stirringthe reaction mixture was stirred at 35° C. for 4 h
  15. filtrationthe mixture was filtered
  16. customto leave a solid
  17. customthat was recrystallised (MeOH)

出典と根拠

ORDレコード
ord-13906fde454341f4803872cc97f1234d
出典データセット
uspto-grants-2010_09
特許番号
US07795283B2

反応ノート

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