Diisopropylethylamine → rac-8-[(3,3-Difluorocyclobutyl)methoxy]-2,6-dimethyl-N-(7,7,7-trifluoro-2-hydroxy-2-methylheptan-3-yl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 1844223노트

반응식

HRID 1844223 반응식
[F:1][C:2]1([F:22])[CH2:5][CH:4]([CH2:6][O:7][C:8]2[C:9]3[N:10]([C:15]([C:19]([OH:21])=O)=[C:16]([CH3:18])[N:17]=3)[CH:11]=[C:12]([CH3:14])[CH:13]=2)[CH2:3]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.Cl.[NH2:57][CH:58]([CH2:63][CH2:64][CH2:65][C:66]([F:69])([F:68])[F:67])[C:59]([CH3:62])([OH:61])[CH3:60]>CN(C=O)C.O>[F:1][C:2]1([F:22])[CH2:5][CH:4]([CH2:6][O:7][C:8]2[C:9]3[N:10]([C:15]([C:19]([NH:57][CH:58]([CH2:63][CH2:64][CH2:65][C:66]([F:67])([F:68])[F:69])[C:59]([OH:61])([CH3:62])[CH3:60])=[O:21])=[C:16]([CH3:18])[N:17]=3)[CH:11]=[C:12]([CH3:14])[CH:13]=2)[CH2:3]1

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86718188rac-3-Amino-7,7,7-trifluoro-2-methylheptan-2-ol hydrochlorideHCID 867181928-[(3,3-Difluorocyclobutyl)methoxy]-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxylic acid

생성물 1

HCID 90115706rac-8-[(3,3-Difluorocyclobutyl)methoxy]-2,6-dimethyl-N-(7,7,7-trifluoro-2-hydroxy-2-methylheptan-3-yl)imidazo[1,2-a]pyridine-3-carboxamide

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

100 mg (0.32 mmol) of 8-[(3,3-difluorocyclobutyl)methoxy]-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxylic acid Example 107A and 135 mg (0.35 mmol) of HATU were initially charged in 2 ml of DMF. 0.16 ml (0.96 mmol) of N,N-diisopropylethylamine and 70.6 mg (0.354 mmol) of rac-3-amino-7,7,7-trifluoro-2-methylheptan-2-ol hydrochloride Example 103A were then added, and the mixture was stirred at RT overnight. 7 ml of water were added, and the reaction solution was extracted twice with 15 ml of ethyl acetate. The combined organic phases were washed with 15 ml of water and with 10 ml of saturated aqueous sodium chloride solution, dried over magnesium sulphate, filtered and concentrated. The residue was purified by preparative RP-HPLC (acetonitrile-water+0.1% formic acid) and the product fractions were combined and concentrated to dryness. This gave 86 mg of the target compound (55% of theory).

후처리

  1. extractionthe reaction solution was extracted twice with 15 ml of ethyl acetate
  2. washThe combined organic phases were washed with 15 ml of water and with 10 ml of saturated aqueous sodium chloride solution
  3. dry with materialdried over magnesium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by preparative RP-HPLC (acetonitrile-water+0.1% formic acid)
  7. concentrationconcentrated to dryness

출처 및 근거

ORD 기록
ord-0eeb58d2b7fb46169e7d780f3bbd3044
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08946215B2

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