O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate → Tert-butyl 2-((2-(4-chloro-3-fluorophenylamino)-2-oxoacetamido)(5-(hydroxymethyl)-4-methylthiazol-2-yl)methyl)piperidine-1-carboxylate

HRID 626611Notes

Reaction equation

HRID 626611 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:13])[C:10]([OH:12])=O)=[CH:4][C:3]=1[F:14].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[C:37]([O:41][C:42]([N:44]1[CH2:49][CH2:48][CH2:47][CH2:46][CH:45]1[CH:50]([NH2:59])[C:51]1[S:52][C:53]([CH2:57][OH:58])=[C:54]([CH3:56])[N:55]=1)=[O:43])([CH3:40])([CH3:39])[CH3:38]>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:13])[C:10]([NH:59][CH:50]([C:51]2[S:52][C:53]([CH2:57][OH:58])=[C:54]([CH3:56])[N:55]=2)[CH:45]2[CH2:46][CH2:47][CH2:48][CH2:49][N:44]2[C:42]([O:41][C:37]([CH3:39])([CH3:40])[CH3:38])=[O:43])=[O:12])=[CH:4][C:3]=1[F:14]

Participants

5

Reactant 3

HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 22934746480451-91-0HCID 712949042-[Amino-(5-hydroxymethyl-4-methyl-thiazol-2-yl)-methyl]-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 57523444Tert-butyl 2-((2-(4-chloro-3-fluorophenylamino)-2-oxoacetamido)(5-(hydroxymethyl)-4-methylthiazol-2-yl)methyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-(4-chloro-3-fluorophenylamino)-2-oxoacetic acid (3′) (0.3 g, 1.378 mmol), TBTU (0.530 g 1.65 mmol) and TEA (0.166 g, 1.65 mmol) in DCM (20 ml) was stirred at RT for 1 h, then 2-[amino-(5-hydroxymethyl-4-methyl-thiazol-2-yl)-methyl]-piperidine-1-carboxylic acid tert-butyl ester (0.470 g, 1.378 mmol) was added and stirring was continued for 6 h. Reaction mixture was washed with 25% aqueous solution of K2CO3 (2×50 ml) and water (50 ml). The product was dried over Na2SO4 and evaporated. The residue was purified by column chromatography on silica gel (EtOAc/hexane1/1) to afford tert-butyl 2-((2-(4-chloro-3-fluorophenylamino)-2-oxoacetamido)(5-(hydroxymethyl)-4-methylthiazol-2-yl)methyl)piperidine-1-carboxylate (4′) (0.53 g, 72%) as a white solid; LC-MS (APCI+) m/z: calcd for C24H30ClFN4O5S: 540.16. found: 541 (M+H+).

Workup

  1. stirringstirring
  2. waitwas continued for 6 h
  3. customReaction mixture
  4. washwas washed with 25% aqueous solution of K2CO3 (2×50 ml) and water (50 ml)
  5. dry with materialThe product was dried over Na2SO4
  6. customevaporated
  7. customThe residue was purified by column chromatography on silica gel (EtOAc/hexane1/1)

Sources & evidence

ORD record
ord-85c153f93ff144259cd8762d94d7a49a
Source dataset
uspto-grants-2016_04
Patent number
US09309237B2

Reaction notes

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