Diisopropylethylamine → 3-[5-(4-cyano-phenyl)-[1,3,4]thiadiazol-2-ylmethyl]-N-((S)-6-morpholin-4-yl-4,5,6,7-tetrahydro-benzothiazol-2-yl)-benzamide

HRID 1468171ノート

反応式

HRID 1468171 の反応式
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[S:13][C:12]([CH2:14][C:15]3[CH:16]=[C:17]([CH:21]=[CH:22][CH:23]=3)[C:18](O)=[O:19])=[N:11][N:10]=2)=[CH:5][CH:4]=1)#[N:2].C(N(CC)C(C)C)(C)C.Br.Br.[N:35]1([C@H:41]2[CH2:50][CH2:49][C:44]3[N:45]=[C:46]([NH2:48])[S:47][C:43]=3[CH2:42]2)[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1.C(=O)(O)[O-].[Na+]>CC(N(C)C)=O.O.C(Cl)CCl>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([C:9]2[S:13][C:12]([CH2:14][C:15]3[CH:16]=[C:17]([CH:21]=[CH:22][CH:23]=3)[C:18]([NH:48][C:46]3[S:47][C:43]4[CH2:42][C@@H:41]([N:35]5[CH2:36][CH2:37][O:38][CH2:39][CH2:40]5)[CH2:50][CH2:49][C:44]=4[N:45]=3)=[O:19])=[N:11][N:10]=2)=[CH:7][CH:8]=1)#[N:2]

参加物

8

反応物 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 675078233-[5-(4-Cyano-phenyl)-[1,3,4]thiadiazol-2-ylmethyl]-benzoic acidHCID 86672750(S)-6-morpholin-4-yl-4,5,6,7-tetrahydro-benzothiazol-2-ylamine dihydrobromide

生成物 1

HCID 569668943-[5-(4-cyano-phenyl)-[1,3,4]thiadiazol-2-ylmethyl]-N-((S)-6-morpholin-4-yl-4,5,6,7-tetrahydro-benzothiazol-2-yl)-benzamide収率 16.5%

試薬・触媒・溶媒 3

HCID 111,2-Dichloroethane溶媒HCID 962Water溶媒HCID 31374Dimethylacetamide溶媒

実験手順

Dissolve 3-[5-(4-cyano-phenyl)-[1,3,4]-thiadiazol-2-ylmethyl]-benzoic acid (0.13 g, 0.28 mmol) in 3 mL of dimethylacetamide. Add N,N-diisopropylethyl amine (0.17 mL, 0.95 mmol), of 7-aza-hydroxybenzotriazole (0.05 g, 0.37 mmol) and EDC (0.07, (0.36 mmol). Stir the mixture at room temperature for 1 h and add (S)-6-morpholin-4-yl-4,5,6,7-tetrahydro-benzothiazol-2-ylamine dihydrobromide (0.14 g, 0.35 mmol) in one portion. Heat the mixture at 60° C. for 15 h. Cool to room temperature and dilute with H2O. Add a saturated aqueous solution of sodium bicarbonate until the pH of the solution is alkaline causing a solid to precipitate from solution. Collect the solid by filtration, wash with H2O and dry on the filter pad. Purify the material by preparative reverse phase HPLC (CH3CN:H2O with 0.1% trifluoroacetic acid) to give 0.025 g, 14% yield of 3-[5-(4-cyano-phenyl)-[1,3,4]thiadiazol-2-ylmethyl]-N—((S)-6-morpholin-4-yl-4,5,6,7-tetrahydro-benzothiazol-2-yl)-benzamide as a solid. MS, ES+ 543.62 (M+H), rt 1.50 min.

後処理

  1. temperatureHeat the mixture at 60° C. for 15 h
  2. temperatureCool to room temperature
  3. customto precipitate from solution
  4. customCollect the solid
  5. filtrationby filtration
  6. washwash with H2O
  7. customdry on the filter pad
  8. customPurify the material by preparative reverse phase HPLC (CH3CN:H2O with 0.1% trifluoroacetic acid)

出典と根拠

ORDレコード
ord-d71a11601a8d402681f26f2b28b2ac08
出典データセット
uspto-grants-2015_04
特許番号
US09000154B2

反応ノート

読み込み中…