Triethylamine → 2-Cyclohexyl-2-[5-fluoro-2-((R)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-N-(4-hydroxy-cyclohexyl)-acetamide

HRID 1170701ノート

反応式

HRID 1170701 の反応式
[CH:1]1([CH:7]([N:11]2[C:15]3[CH:16]=[CH:17][C:18]([F:20])=[CH:19][C:14]=3[N:13]=[C:12]2[C@H:21]([O:28][CH3:29])[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:8](O)=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[NH2:62][C@H:63]1[CH2:68][CH2:67][C@H:66]([OH:69])[CH2:65][CH2:64]1>CN(C=O)C>[CH:1]1([CH:7]([N:11]2[C:15]3[CH:16]=[CH:17][C:18]([F:20])=[CH:19][C:14]=3[N:13]=[C:12]2[C@H:21]([O:28][CH3:29])[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:8]([NH:62][CH:63]2[CH2:68][CH2:67][CH:66]([OH:69])[CH2:65][CH2:64]2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

参加物

6

反応物 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66810397Cyclohexyl-[5-fluoro-2-((R)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-acetic acidHCID 178479278HCID 178479278、化合物

生成物 1

HCID 673723982-Cyclohexyl-2-[5-fluoro-2-((R)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-N-(4-hydroxy-cyclohexyl)-acetamide収率 40.5%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
40 °C

実験手順

To a solution of cyclohexyl-[5-fluoro-2-((R)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-acetic acid (100 mg, 0.25 mmol, 1.0 equiv) in DMF (1.5 mL) was added triethylamine (51.1 mg, 70.0 μL, 0.50 mmol, 2.0 equiv) and HATU (124.7 mg, 0.33 mmol, 1.3 equiv) and the mixture stirred at 40° C. After 15 min, trans-4-amino-cyclohexanol hydrochloride (50.03 mg, 0.33 mmol, 1.3 equiv; [CAS RN 50910-54-8]) was added and stirring continued at 50° C. for 2 h. Removal of the solvent mixture under reduced pressure and purification by preparative HPLC on reversed phase eluting with a gradient of acetonitrile/water provided 50 mg (40%) of the title compound.

後処理

  1. stirringstirring
  2. waitcontinued at 50° C. for 2 h
  3. customRemoval of the solvent mixture
  4. customunder reduced pressure and purification by preparative HPLC on reversed phase
  5. washeluting with a gradient of acetonitrile/water

出典と根拠

ORDレコード
ord-682ee0d282644ab18f7503c4bc33afd4
出典データセット
uspto-grants-2010_11
特許番号
US07825258B2

反応ノート

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