1-Hydroxybenzotriazole → rac-{1-[({7-[(2,6-Difluorobenzyl)oxy]-2-methylpyrazolo[1,5-a]pyridin-3-yl}carbonyl)amino]-2-methylpentan-2-yl}carbamic Acid tert-butyl Ester

HRID 1486297노트

반응식

HRID 1486297 반응식
[F:1][C:2]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:3]=1[CH2:4][O:5][C:6]1[N:11]2[N:12]=[C:13]([CH3:18])[C:14]([C:15]([OH:17])=O)=[C:10]2[CH:9]=[CH:8][CH:7]=1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[C:46]([O:50][C:51](=[O:60])[NH:52][C:53]([CH3:59])([CH2:56][CH2:57][CH3:58])[CH2:54][NH2:55])([CH3:49])([CH3:48])[CH3:47].C(N(CC)C(C)C)(C)C>O1CCCC1>[C:46]([O:50][C:51](=[O:60])[NH:52][C:53]([CH3:59])([CH2:56][CH2:57][CH3:58])[CH2:54][NH:55][C:15]([C:14]1[C:13]([CH3:18])=[N:12][N:11]2[C:6]([O:5][CH2:4][C:3]3[C:2]([F:1])=[CH:22][CH:21]=[CH:20][C:19]=3[F:23])=[CH:7][CH:8]=[CH:9][C:10]=12)=[O:17])([CH3:49])([CH3:48])[CH3:47]

참가 물질

7

반응물 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 84723920rac-tert-Butyl (1-amino-2-methylpentan-2-yl)carbamateHCID 1178595867-[(2,6-Difluorobenzyl)oxy]-2-methylpyrazolo[1,5-a]pyridine-3-carboxylic Acid

생성물 1

HCID 121434576rac-{1-[({7-[(2,6-Difluorobenzyl)oxy]-2-methylpyrazolo[1,5-a]pyridin-3-yl}carbonyl)amino]-2-methylpentan-2-yl}carbamic Acid tert-butyl Ester

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

A solution of 100 mg (0.19 mmol, 61% pure) of 7-[(2,6-difluorobenzyl)oxy]-2-methylpyrazolo[1,5-a]pyridine-3-carboxylic acid from Example 130A in 4 ml of tetrahydrofuran was admixed with 39.1 mg (0.287 mmol) of 1-hydroxybenzotriazole and 74.3 mg (0.287 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. The resulting solution was stirred at room temperature for 15 min, and then 62.2 mg (0.287 mmol) of rac-(1-amino-2-methylpentan-2-yl)carbamic acid tert-butyl ester from Example 152A were added, followed by 0.1 ml (0.575 mmol) of N,N-diisopropylethylamine After the addition, the mixture was stirred at room temperature for a further 15 h. The solvent was drawn off under reduced pressure and the residue was partitioned between dichloromethane (10 ml) and water (10 ml). The organic phase was removed and washed with water and saturated aqueous sodium chloride solution, dried with a phase separation cartridge and concentrated under reduced pressure, which gave 45 mg (24% of theory, 53% pure) of the target compound.

후처리

  1. additionAfter the addition
  2. stirringthe mixture was stirred at room temperature for a further 15 h
  3. customthe residue was partitioned between dichloromethane (10 ml) and water (10 ml)
  4. customThe organic phase was removed
  5. washwashed with water and saturated aqueous sodium chloride solution
  6. customdried with a phase separation cartridge
  7. concentrationconcentrated under reduced pressure, which
  8. customgave 45 mg (24% of theory, 53% pure) of the target compound

출처 및 근거

ORD 기록
ord-459c0a2febc7489791175589b636213e
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09422285B2

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