Diisopropylethylamine → 2-(2-Tosyl-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-1-yl)-N-((R)-6-((2,2,2-trifluoroethylamino)methyl)-1,2,3,4-tetrahydronaphthalen-1-yl)acetamide

HRID 1694321ノート

反応式

HRID 1694321 の反応式
[S:1]([N:11]1[CH2:16][CH2:15][N:14]2[CH:17]=[CH:18][CH:19]=[C:13]2[CH:12]1[CH2:20][C:21]([OH:23])=O)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:57][C:58]([F:74])([F:73])[CH2:59][NH:60][CH2:61][C:62]1[CH:63]=[C:64]2[C:69](=[CH:70][CH:71]=1)[C@H:68]([NH2:72])[CH2:67][CH2:66][CH2:65]2>C1COCC1>[S:1]([N:11]1[CH2:16][CH2:15][N:14]2[CH:17]=[CH:18][CH:19]=[C:13]2[CH:12]1[CH2:20][C:21]([NH:72][C@H:68]1[C:69]2[C:64](=[CH:63][C:62]([CH2:61][NH:60][CH2:59][C:58]([F:57])([F:73])[F:74])=[CH:71][CH:70]=2)[CH2:65][CH2:66][CH2:67]1)=[O:23])([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:2])=[O:3]

参加物

6

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 59486384(R)-6-((2,2,2-Trifluoroethylamino)methyl)-1,2,3,4-tetrahydronaphthalen-1-amineHCID 59486400HCID 59486400、化合物

生成物 1

HCID 469085002-(2-Tosyl-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-1-yl)-N-((R)-6-((2,2,2-trifluoroethylamino)methyl)-1,2,3,4-tetrahydronaphthalen-1-yl)acetamide収率 22%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a solution of 2-(2-tosyl-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-1-yl)acetic acid (S11) (214 mg, 0.64 mmol, 1.0 eq.) in THF (5 ml) were added DIPEA (340 μl, 1.92 mmol, 3.0 eq.) and HATU (292 mg, 0.77 mmol, 1.2 eq.) at 0° C. and the mixture was stirred for 15 min at the same temperature. A solution of (R)-6-((2,2,2-trifluoroethylamino)methyl)-1,2,3,4-tetrahydronaphthalen-1-amine (A53) (0.64 mmol, 1.0 eq.) in THF (5 ml) was added to the reaction mixture and it was stirred at RT for 16 h. The reaction mixture was concentrated and the residue was diluted with DCM (50 ml) and washed with sat. NH4Cl solution (20 ml), sat. NaHCO3 solution (20 ml), water (20 ml) and brine (20 ml). The organic layer was dried over Na2SO4 and concentrated under reduced pressure to give the crude product which was purified by column chromatography (silica gel; 0.7% MeOH/DCM) to yield the desired product as an off-white solid. Yield: 22% (80 mg, 0.14 mmol); MS, Rt=3.2 min; m/z=575.0 [MH]+

後処理

  1. stirringwas stirred at RT for 16 h
  2. concentrationThe reaction mixture was concentrated
  3. additionthe residue was diluted with DCM (50 ml)
  4. washwashed with sat. NH4Cl solution (20 ml), sat. NaHCO3 solution (20 ml), water (20 ml) and brine (20 ml)
  5. dry with materialThe organic layer was dried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customto give the crude product which
  8. customwas purified by column chromatography (silica gel; 0.7% MeOH/DCM)

出典と根拠

ORDレコード
ord-0f932903c66a497c853dae197a2bd397
出典データセット
uspto-grants-2012_04
特許番号
US08158628B2

反応ノート

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