Diisopropylethylamine → tert-butyl 4-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1,3,5-triazin-2-yl]-1-piperazinecarboxylate

HRID 1256504ノート

反応式

HRID 1256504 の反応式
Cl[C:2]1[N:7]=[C:6]([N:8]2[C:12]3[CH:13]=[CH:14][CH:15]=[C:16]([O:17][CH3:18])[C:11]=3[N:10]=[C:9]2[CH:19]([F:21])[F:20])[N:5]=[C:4]([N:22]2[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]2)[N:3]=1.Cl.[CH:36]12[O:43][CH:40]([CH2:41][CH2:42]1)[CH2:39][NH:38][CH2:37]2.CCN(C(C)C)C(C)C>C1COCC1>[F:20][CH:19]([F:21])[C:9]1[N:8]([C:6]2[N:7]=[C:2]([N:38]3[CH2:37][CH:36]4[O:43][CH:40]([CH2:41][CH2:42]4)[CH2:39]3)[N:3]=[C:4]([N:22]3[CH2:23][CH2:24][N:25]([C:28]([O:30][C:31]([CH3:32])([CH3:34])[CH3:33])=[O:29])[CH2:26][CH2:27]3)[N:5]=2)[C:12]2[CH:13]=[CH:14][CH:15]=[C:16]([O:17][CH3:18])[C:11]=2[N:10]=1

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 219835368-Oxa-3-aza-bicyclo(3.2.1)octane hydrochlorideHCID 86645856tert-butyl 4-(4-chloro-6-(2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl)-1,3,5-triazin-2-yl)piperazine-1-carboxylate

生成物 1

HCID 67546680tert-butyl 4-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1,3,5-triazin-2-yl]-1-piperazinecarboxylate収率 85%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

A mixture of tert-butyl 4-{4-chloro-6-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-1,3,5-triazin-2-yl}-1-piperazinecarboxylate (550 mg, 1.11 mmol), 8-oxa-3-azabicyclo[3.2.1]octane hydrochloride (215 mg, 1.44 mmol) and DIPEA (0.77 mL, 4.44 mmol) in THF (20 mL) was stirred at room temperature overnight. The solvent was removed under vacuum and the residue diluted with water. The resulting precipitate was washed with water, dissolved in CH2Cl2, dried (Na2SO4) and recrystallized from CH2Cl2/MeOH to give 540 mg (85% yield) of tert-butyl 4-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1,3,5-triazin-2-yl]-1-piperazinecarboxylate: mp (CH2Cl2/MeOH) 181-183° C.; 1H NMR (CDCl3) δ7.89 (dd, J=8.4, 0.6 Hz, 1H), 7.49 (t, JHF=53.6 Hz, 1H), 7.35 (t, J=8.2 Hz, 1H), 6.81 (d, J=7.6, 1H), 4.48 (d, J=8.0 Hz, 2H), 4.33 (dd, J=12.6, 8.9 Hz, 2H), 4.05 (s, 3H), 3.87 (br s, 4H), 3.53 (br s, 4H), 3.29 (ddd, J=32.8, 13.1, 1.6 Hz, 2H), 1.99 (dd, J=8.3, 4.4 Hz, 2H), 1.79 (m, 2H), 1.50 (s, 9H); Anal. Calcd. for C27H34F2N8O4.0.05H2O: C, 56.55; H, 6.0; N, 19.5. Found: C, 56.2; H, 6.0; N, 19.6.

後処理

  1. customThe solvent was removed under vacuum
  2. additionthe residue diluted with water
  3. washThe resulting precipitate was washed with water
  4. dissolutiondissolved in CH2Cl2
  5. dry with materialdried (Na2SO4)
  6. customrecrystallized from CH2Cl2/MeOH

出典と根拠

ORDレコード
ord-591075fc23ee4b13a8d9ec03282ece15
出典データセット
uspto-grants-2013_06
特許番号
US08461158B2

反応ノート

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