1,2-Dichloroethane → methyl 2-(4-{(S)-{[(4-tert-butylphenyl)-acetyl]amino}[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}-1H-1,2,3-triazol-1-yl)-2-methylpropanoate

HRID 877360Notes

Reaction equation

HRID 877360 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]([OH:14])=O)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[Cl-].[CH3:16][O:17][C:18](=[O:41])[C:19]([N:22]1[CH:26]=[C:25]([C@H:27]([C:29]2[CH:34]=[CH:33][C:32]([O:35][CH2:36][C:37]([F:40])([F:39])[F:38])=[CH:31]C=2)[NH3+:28])[N:24]=[N:23]1)([CH3:21])[CH3:20].C1C=[N:46]C2N(O)N=NC=2C=1.C(Cl)CCl.C(N(CC)CC)C>C(Cl)Cl>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([CH2:11][C:12]([NH:28][C@H:27]([C:29]2[CH:34]=[CH:33][C:32]([O:35][CH2:36][C:37]([F:39])([F:38])[F:40])=[CH:31][N:46]=2)[C:25]2[N:24]=[N:23][N:22]([C:19]([CH3:20])([CH3:21])[C:18]([O:17][CH3:16])=[O:41])[CH:26]=2)=[O:14])=[CH:9][CH:10]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 118343Benzeneacetic acid, 4-(1,1-dimethylethyl)-HCID 181649HOAtHCID 86668960(S)-[1-(2-methoxy-1,1-dimethyl-2-oxoethyl)-1H-1,2,3-triazol-4-yl][4-(2,2,2-trifluoroethoxy)phenyl]methanaminium chloride

Product 1

HCID 68156240methyl 2-(4-{(S)-{[(4-tert-butylphenyl)-acetyl]amino}[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}-1H-1,2,3-triazol-1-yl)-2-methylpropanoateYield 42.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 0.05 g (0.26 mmol) (4-tert-butylphenyl)acetic acid in 0.50 ml CH2Cl2 was added 0.12 g (0.26 mmol) (S)-[1-(2-methoxy-1,1-dimethyl-2-oxoethyl)-1H-1,2,3-triazol-4-yl][4-(2,2,2-trifluoroethoxy)phenyl]methanaminium chloride, 0.05 g (0.34 mmol) HOAT, 0.07 g (0.34 mmol) EDC, and 0.14 ml (0.78 mmol) triethylamine. After 1 h at room temperature, the reaction mixture was diluted with CH2Cl2, and washed twice with water. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. Purification by preparative HPLC (5->95% CH3CN/H2O over 15 min, 0.05% added TFA, C18) afforded 0.06 g (42%) methyl 2-(4-{(S)-{[(4-tert-butylphenyl)acetyl]amino}[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}-1H-1,2,3-triazol-1-yl)-2-methylpropanoate. ES-MS [M+1]+=548.3.

Workup

  1. washwashed twice with water
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customPurification
  6. additionby preparative HPLC (5->95% CH3CN/H2O over 15 min, 0.05% added TFA, C18)

Sources & evidence

ORD record
ord-f3898318f89545faa80dbb31d13d2a67
Source dataset
uspto-grants-2015_03
Patent number
US08987310B2

Reaction notes

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