Toluene → 2-(2-Amino-1,3-thiazol-4-yl)-N-[2-bromo-4-({(2R,5R)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidin-2-yl}methyl)phenyl]acetamide

HRID 243744ノート

反応式

HRID 243744 の反応式
[NH2:1][C:2]1[S:3][CH:4]=[C:5]([CH2:7][C:8]([NH:10][C:11]2[CH:37]=[CH:36][C:14]([CH2:15][C@H:16]3[CH2:20][CH2:19][C@H:18]([C@H:21]([OH:28])[C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[N:17]3C(OC(C)(C)C)=O)=[CH:13][C:12]=2[Br:38])=[O:9])[N:6]=1.C(O)(C(F)(F)F)=O.C1(C)C=CC=CC=1>C(Cl)Cl.C(#N)C.O.CO>[NH2:1][C:2]1[S:3][CH:4]=[C:5]([CH2:7][C:8]([NH:10][C:11]2[CH:37]=[CH:36][C:14]([CH2:15][C@H:16]3[CH2:20][CH2:19][C@H:18]([C@H:21]([OH:28])[C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=4)[NH:17]3)=[CH:13][C:12]=2[Br:38])=[O:9])[N:6]=1

参加物

6

反応物 3

HCID 1140TolueneHCID 6422Trifluoroacetic acidHCID 57907418Tert-butyl (2R,5R)-2-(4-{[(2-amino-1,3-thiazol-4-yl)acetyl]amino}-3-bromobenzyl)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidine-1-carboxylate

生成物 1

HCID 579075972-(2-Amino-1,3-thiazol-4-yl)-N-[2-bromo-4-({(2R,5R)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidin-2-yl}methyl)phenyl]acetamide収率 90.1%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 21864137Acetonitrile methanol water溶媒

実験手順

To a solution of 75 mg (0.124 mmol) of tert-butyl (2R,5R)-2-(4-{[(2-amino-1,3-thiazol-4-yl)acetyl]amino}-3-bromobenzyl)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidine-1-carboxylate (from Step A, Example 313) in 2.0 mL DCM was added 1.0 mL TFA and the reaction mixture stirred at room temperature for 2 h. Azeotrop with toluene (2×) to excess acid. The residue was then taken up in acetonitrile/water/MeOH (9:1:1) and purified on the Gilson HPLC eluting with a 10-90% gradient of acetonitrile/water with 0.05% TFA buffer. The fractions containing the product were combined, frozen, and lyophilized to give a white foam (56 mg, 90%). m/z (ES) 501(M)+ and 503 (M+2)+, also 523 (MNa)+and 525 (MNa+2)+.

後処理

  1. custompurified on the Gilson HPLC
  2. washeluting with a 10-90% gradient of acetonitrile/water with 0.05% TFA buffer
  3. additionThe fractions containing the product
  4. temperaturefrozen

出典と根拠

ORDレコード
ord-7664c302f93442bbb13dec1bfd033fbe
出典データセット
uspto-grants-2014_02
特許番号
US08653260B2

反応ノート

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