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

HRID 243742Notes

Reaction equation

HRID 243742 reaction equation
[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

Participants

6

Reactant 3

HCID 1140TolueneHCID 6422Trifluoroacetic acidHCID 57907380Tert-butyl (2S,5R)-2-(4-{[(2-amino-1,3-thiazol-4-yl)acetyl]amino}-3-bromobenzyl)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidine-1-carboxylate

Product 1

HCID 579074742-(2-Amino-1,3-thiazol-4-yl)-N-[2-bromo-4-({(2S,5R)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidin-2-yl}methyl)phenyl]acetamideYield 88%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21864137Acetonitrile methanol waterSolvent

Procedure

To a solution of 105 mg (0.175 mmol) of tert-butyl (2S,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) 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 (77 mg, 88%). m/z (ES) 501(M)+ and 503 (M+2)+, also 523 (MNa)+and 525 (MNa+2)+.

Workup

  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

Sources & evidence

ORD record
ord-e849a15e2efd442c877e76eb369d9d19
Source dataset
uspto-grants-2014_02
Patent number
US08653260B2

Reaction notes

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