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 1990202ノート

反応式

HRID 1990202 の反応式
[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

参加物

7

反応物 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

生成物 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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

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)+

後処理

  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)

出典と根拠

ORDレコード
ord-ec8b96660d5848d4b52f40da3fe3fac2
出典データセット
uspto-grants-2010_01
特許番号
US07642259B2

反応ノート

読み込み中…