Diisopropylethylamine → 3-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-{[(1S)-1-(hydroxymethyl)propyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide

HRID 1990202노트

반응식

HRID 1990202 반응식
[OH:1][CH2:2][C@@H:3]([O:6][C:7]1[CH:8]=[C:9]([O:22][C:23]2[N:24]=[CH:25][C:26]([C:29](O)=[O:30])=[N:27][CH:28]=2)[CH:10]=[C:11]([C:13]([NH:15][C:16]2[CH:20]=[CH:19][N:18]([CH3:21])[N:17]=2)=[O:14])[CH:12]=1)[CH2:4][CH3:5].Cl.[NH:33]1[CH2:36][CH2:35][CH2:34]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.O>[N:33]1([C:29]([C:26]2[N:27]=[CH:28][C:23]([O:22][C:9]3[CH:10]=[C:11]([CH:12]=[C:7]([O:6][C@H:3]([CH2:2][OH:1])[CH2:4][CH3:5])[CH:8]=3)[C:13]([NH:15][C:16]3[CH:20]=[CH:19][N:18]([CH3:21])[N:17]=3)=[O:14])=[N:24][CH:25]=2)=[O:30])[CH2:36][CH2:35][CH2:34]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 12308726Azetidine hydrochlorideHCID 536296535-[(3-{[(1S)-1-(hydroxymethyl)propyl]oxy}-5-{[(1-methyl-1H-pyrazol-3-yl)amino]carbonyl}phenyl)oxy]pyrazine-2-carboxylic acid

생성물 1

HCID 160397613-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-{[(1S)-1-(hydroxymethyl)propyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

A solution of 5-[(3-{[(1S)-1-(hydroxymethyl)propyl]oxy}-5-{[(1-methyl-1H-pyrazol-3-yl)amino]carbonyl}phenyl)oxy]pyrazine-2-carboxylic acid (12 mg, 0.03 mmol), azetidine hydrochloride (4 mg, 0.06 mmol), HATU (14 mg, 0.04 mmol) and DIPEA (0.02 mL, 0.11 mmol) in DMF (1 mL) was stirred at RT over the weekend. Water (15 mL) was added and the solution extracted with ethyl acetate (25 mL). The ethyl acetate layer was washed with brine (20 mL), dried (MgSO4), and evaporated to a residue which was chromatographed by preparative HPLC on C18 reversed phase, eluting with 5-95% acetonitrile (+0.2% TFA) in water (+0.2% TFA), to give the required product along with 15% of a co-eluting impurity (5 mg). 1H NMR δ (CDCl3): 0.92 (t, 3H), 0.97 (t, 0.45H), 1.69 (quin, 2H), 1.76 (m, 0.3H), 2.34 (quin, 2H), 3.76 (m, 2H), 3.86 (s, 3H), 4.23 (t, 2H), 4.49 (sextet, 1H), 4.66 (t, 2H), 4.77 (m, 0.15H), 6.93 (t, 1H), 6.99 (d, 1H), 7.34 (s, 1H), 7.46 (s, 1H), 7.50 (s, 1H), 8.29 (s, 1H), 8.78 (s, 1H), 10.68 (s, 1H), 10.78 (s, 0.15H); m/z 468 (M+H)+

후처리

  1. extractionthe solution extracted with ethyl acetate (25 mL)
  2. washThe ethyl acetate layer was washed with brine (20 mL)
  3. dry with materialdried (MgSO4)
  4. customevaporated to a residue which
  5. customwas chromatographed by preparative HPLC on C18 reversed phase
  6. washeluting with 5-95% acetonitrile (+0.2% TFA) in water (+0.2% TFA)

출처 및 근거

ORD 기록
ord-ec8b96660d5848d4b52f40da3fe3fac2
출처 데이터셋
uspto-grants-2010_01
특허 번호
US07642259B2

반응 노트

불러오는 중…