Triethylamine → Pf-5190457

HRID 2205093ノート

反応式

HRID 2205093 の反応式
Cl.Cl.[CH3:3][C:4]1[N:9]=[CH:8][N:7]=[C:6]([C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[C@H:15]([N:19]2[CH2:22][C:21]4([CH2:27][CH2:26][NH:25][CH2:24][CH2:23]4)[CH2:20]2)[CH2:14][CH2:13]3)[CH:5]=1.C(N(CC)CC)C.Cl.[CH3:36][C:37]1[S:41][C:40]2=[N:42][C:43]([CH2:45][C:46](O)=[O:47])=[CH:44][N:39]2[CH:38]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl.CN(C=O)C>[CH3:36][C:37]1[S:41][C:40]2=[N:42][C:43]([CH2:45][C:46]([N:25]3[CH2:26][CH2:27][C:21]4([CH2:22][N:19]([C@H:15]5[C:16]6[C:12](=[CH:11][C:10]([C:6]7[CH:5]=[C:4]([CH3:3])[N:9]=[CH:8][N:7]=7)=[CH:18][CH:17]=6)[CH2:13][CH2:14]5)[CH2:20]4)[CH2:23][CH2:24]3)=[O:47])=[CH:44][N:39]2[CH:38]=1

参加物

7

反応物 4

HCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67405889HCID 67405889、化合物HCID 674062952-[(R)-5-(6-methyl-pyrimidin-4-yl)-indan-1-yl]-2,7-diaza-spiro[3.5]nonane dihydrochloride

生成物 1

HCID 58438464Pf-5190457

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒2 回

反応条件

温度
100 °C

実験手順

To a suspension of 2-[(R)-5-(6-methyl-pyrimidin-4-yl)-indan-1-yl]-2,7-diaza-spiro[3.5]nonane dihydrochloride (540 mg, 1.22 mmol) in 10 mL of dichloromethane was added triethylamine (492 mg, 4.90 mmol). Once the mixture became a homogenous solution, it was added to a solution of 2-(2-methylimidazo[2,1-b]thiazol-6-yl)acetic acid hydrochloride (251 mg, 1.28 mmol) in 3 mL of dichloromethane. The mixture was stirred for 5 minutes and HBTU (462 mg, 1.22 mmol) in 2 mL of DMF was added. The reaction was stirred at room temperature for 1.5 hours. The reaction was quenched by the addition of 10 mL of NaHCO3 and was diluted with 50 mL of dichloromethane. The organic layer was washed with saturated brine, dried over Na2SO4, filtered and the filtrate was concentrated. The residue was dissolved in 5 mL of CH3CN and the solution was heated to 100° C. for 1 hour with stirring. The mixture was cooled to room temperature and the resulting solids were vacuum filtered to afford the desired product as an off white powder (428 mg, 69%). MS (ES+) 513.5 (M+H)+. 1H NMR (CD3OD) δ 1.70-1.74 (m, 4H), 1.88-1.96 (m, 1H), 2.27-2.34 (m, 2H), 2.40 (s, 3H), 2.58 (s, 3H), 2.86-2.97 (m, 1H), 3.11-3.15 (m, 1H), 3.31-3.34 (m, 3H), 3.52-3.55 (m, 4H), 3.78 (s, 2H), 4.05-4.09 (m, 1H), 7.33 (s, 2H), 7.55 (d, 1H), 7.78-7.79 (m, 1H), 7.94-8.03 (m, 2H), 8.93 (s, 1H). [α]D20=+45.3 deg (c=2.5 mg/mL, MeOH).

後処理

  1. stirringThe reaction was stirred at room temperature for 1.5 hours
  2. customThe reaction was quenched by the addition of 10 mL of NaHCO3
  3. additionwas diluted with 50 mL of dichloromethane
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated
  8. dissolutionThe residue was dissolved in 5 mL of CH3CN
  9. stirringwith stirring
  10. temperatureThe mixture was cooled to room temperature
  11. filtrationfiltered

出典と根拠

ORDレコード
ord-b7c87b645d314e21b925e9b798d7f512
出典データセット
uspto-grants-2016_06
特許番号
US09370516B2

反応ノート

読み込み中…