Lithium → (2R)-N-((1S,2R)-3-(((4S)-6-bromo-3,4-dihydrospiro[chromene-2,1'-cyclobutan]-4-yl)amino)-2-hydroxy-1-(phenylmethyl)propyl)-4-((4-propyl-1H-1,2,3-triazol-1-yl)acetyl)-2-morpholinecarboxamide

HRID 253148

反応式

HRID 253148 の反応式
[CH2:1]([C:4]1[N:5]=[N:6][N:7]([CH2:9][C:10]([N:12]2[CH2:17][CH2:16][O:15][CH:14]([C:18]([OH:20])=O)[CH2:13]2)=[O:11])[CH:8]=1)[CH2:2][CH3:3].[Li].[NH2:22][C@@H:23]([CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[C@H:24]([OH:40])[CH2:25][NH:26][C@@H:27]1[C:36]2[C:31](=[CH:32][CH:33]=[C:34]([Br:37])[CH:35]=2)[O:30][C:29]([CH3:39])([CH3:38])[CH2:28]1.[CH3:48]N(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Br:37][C:34]1[CH:35]=[C:36]2[C:31](=[CH:32][CH:33]=1)[O:30][C:29]1([CH2:39][CH2:48][CH2:38]1)[CH2:28][C@@H:27]2[NH:26][CH2:25][C@@H:24]([OH:40])[C@@H:23]([NH:22][C:18]([C@@H:14]1[O:15][CH2:16][CH2:17][N:12]([C:10](=[O:11])[CH2:9][N:7]2[CH:8]=[C:4]([CH2:1][CH2:2][CH3:3])[N:5]=[N:6]2)[CH2:13]1)=[O:20])[CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1

参加物

6

反応物 4

HCID 3028194LithiumHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66844876(2R,3S)-3-amino-1-((S)-6-bromo-2,2-dimethylchroman-4-ylamino)-4-phenylbutan-2-olHCID 668453864-(2-(4-propyl-1H-1,2,3-triazol-1-yl)acetyl)morpholine-2-carboxylic acid

生成物 1

HCID 66844854(2R)-N-((1S,2R)-3-(((4S)-6-bromo-3,4-dihydrospiro[chromene-2,1'-cyclobutan]-4-yl)amino)-2-hydroxy-1-(phenylmethyl)propyl)-4-((4-propyl-1H-1,2,3-triazol-1-yl)acetyl)-2-morpholinecarboxamide

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

In a 15-mL RBF, the 4-(2-(4-propyl-1H-1,2,3-triazol-1-yl)acetyl)morpholine-2-carboxylic acid (0.034 g, 0.11 mmol) as the crude lithium salt and (2R,3S)-3-amino-1-((S)-6-bromo-2,2-dimethylchroman-4-ylamino)-4-phenylbutan-2-ol (0.046 g, 0.11 mmol) were taken up in DMF (1.5 mL). When the solids had dissolved, HATU (0.041 g, 0.11 mmol) was added. After 14 h, the reaction was concentrated, and the residue was taken up in EtOAc (60 mL) and the organic layer was extracted with water (5 mL), dried over sodium sulfate and concentrated. The residue was purified through silica gel (15 mL) which had been deactivated with TEA (2.0 mL) eluting with 4% MeOH-EtOAc, to afford the title compound as a 1:1 mixture of diastereomers. MS m/z 695/697 (M+1).

後処理

  1. dissolutionWhen the solids had dissolved
  2. concentrationthe reaction was concentrated
  3. extractionthe organic layer was extracted with water (5 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified through silica gel (15 mL) which
  7. washeluting with 4% MeOH-EtOAc

出典と根拠

ORDレコード
ord-3d10066892cb490d890fafe962ab9915
出典データセット
uspto-grants-2011_01
特許番号
US07872009B2

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