Triethylamine → HCID 178434276, 화합물

HRID 537194노트

반응식

HRID 537194 반응식
Cl.C([N:6]1[CH:14]=[C:13]2[C:8]([C:9](=[O:22])[NH:10][C:11]3([CH2:20][CH:19]4[NH:21][CH:16](CC4)[CH2:15]3)[CH2:12]2)=[N:7]1)(C)(C)C.[CH3:23][C:24]1[C:32]2[C:27](=[C:28]([CH3:36])[CH:29]=[C:30]([C:33]([OH:35])=O)[CH:31]=2)[NH:26][N:25]=1.C(N(CC)CC)C.[CH3:44][CH2:45][CH2:46]P1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>CN(C)C=O.CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[CH3:23][C:24]1[C:32]2[C:27](=[C:28]([CH3:36])[CH:29]=[C:30]([C:33]([N:21]3[CH2:16][CH2:15][C:11]4([NH:10][C:9](=[O:22])[C:8]5[N:7]([CH:45]([CH3:46])[CH3:44])[N:6]=[CH:14][C:13]=5[CH2:12]4)[CH2:20][CH2:19]3)=[O:35])[CH:31]=2)[NH:26][N:25]=1

참가 물질

8

반응물 4

HCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 674914372'-tert-butyl-4',6'-dihydro-8-azaspiro[bicyclo[3.2.1]octane-3,5'-pyrazolo[3,4-c]pyridin]-7'(2'H)-one hydrochloride2회HCID 178434277HCID 178434277, 화합물

생성물 1

HCID 178434276HCID 178434276, 화합물수율 25.2%

시약·촉매·용매 3

HCID 142844-(Dimethylamino)pyridine촉매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 1′-isopropyl-4′,6′-dihydrospiro[piperidine-4,5′-pyrazolo[3,4-c]pyridin]-7′(1H)-one hydrochloride salt (Intermediate 2, 430 mg, 1.3 mmol) and 3,7-dimethyl-1H-indazole-5-carboxylic acid (306 mg, 1.6 mmol) in dimethylformamide (2 mL) was added triethylamine (0.75 mL, 5.4 mmol), 4-dimethylaminopyridine (33 mg, 0.37 mmol), and 1-propanephosphonic acid cyclic anhydride (0.52 mL, 1.74 mmol, 50% solution in ethyl acetate), and the reaction mixture was stirred overnight at room temperature. The reaction mixture was concentrated in vacuo, taken up in ethyl acetate and washed with saturated aqueous sodium bicarbonate. The organic layer was dried over sodium sulfate, filtered, and concentrated to a solid. The solid was purified via flash column chromatography (0-15% methanol/dichloromethane) to afford a glassy solid. The glassy solid was stirred in ethyl acetate for 16 hours and the resulting solid collected by vacuum filtration to afford the desired product as a white solid (138 mg). +ESI (M+H) 421.0; 1H NMR (400 MHz, CD3OD, δ): 7.65 (s, 1H) 7.42 (s, 1H) 7.21 (s, 1H) 5.50 (m, 1H) 3.95 (br. s., 1H) 3.50-3.62 (br. s., 3H) 2.97 (s, 2H) 2.56 (m, 6H) 1.83 (br. s., 4H) 1.44 (d, 6H).

후처리

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. washwashed with saturated aqueous sodium bicarbonate
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to a solid
  6. customThe solid was purified via flash column chromatography (0-15% methanol/dichloromethane)
  7. customto afford a glassy solid
  8. filtrationthe resulting solid collected by vacuum filtration

출처 및 근거

ORD 기록
ord-15ce9741487f4c8a8eaea116690541e8
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08859773B2

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