1,2-Dichloroethane → HCID 178428308, compound

HRID 928142Notes

Reaction equation

HRID 928142 reaction equation
[OH:1][CH:2]([C:12]1[S:13][C:14]([C:17]2[CH:22]=[C:21]([NH:23][C:24]3[N:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][N:25]=3)[CH:20]=[C:19]([CH3:34])[CH:18]=2)=[CH:15][N:16]=1)[C@@H:3]1[CH2:8][CH2:7][C@H:6]([C:9](O)=[O:10])[CH2:5][CH2:4]1.C(Cl)CCl.C1C=CC2N(O)N=[N:45]C=2C=1.C(N(C(C)C)CC)(C)C.[Cl-].[NH4+]>CN(C=O)C.O>[OH:1][CH:2]([C:12]1[S:13][C:14]([C:17]2[CH:22]=[C:21]([NH:23][C:24]3[N:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][N:25]=3)[CH:20]=[C:19]([CH3:34])[CH:18]=2)=[CH:15][N:16]=1)[C@@H:3]1[CH2:4][CH2:5][C@H:6]([C:9]([NH2:45])=[O:10])[CH2:7][CH2:8]1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 178428309HCID 178428309, compound

Product 1

HCID 178428308HCID 178428308, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of cis-4-{hydroxy[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]methyl}cyclohexanecarboxylic acid (24 mg, 0.049 mmol), EDC (19 mg, 0.097 mmol), HOBt (13 mg, 0.097 mmol) and diisopropylethyl amine (51 uL, 0.292 mmol) in DMF (1 mL) was added ammonium chloride (7.8 mg, 0.15 mmol) and the mixture was stirred at room temperature for 16 h. The solution was then diluted with water and extracted with ethyl acetate (3×). The organic layers were combined, dried with magnesium sulfate, filtered and concentrated. The residue was purified by column chromatography to afford cis-4-{hydroxy[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]methyl}cyclohexanecarboxamide as a white solid. MS ESI calc'd. for C23H25F3N5O2S [M+H]+ 492. found 492. 1H NMR (500 MHz, DMSO-d6) δ 10.25 (s, 1H), 8.83 (d, J=4.9, 1H), 7.96 (s, 2H), 7.45 (s, 1H), 7.27 (d, J=4.9, 1H), 7.16 (s, 1H), 7.13 (s, 1H), 6.68 (s, 1H), 6.14 (d, J=4.9, 1H), 4.76-4.56 (m, 1H), 3.15 (d, J=5.2, 1H), 2.31 (s, 3H), 2.24 (s, 1H), 1.86 (d, J=5.9, 2H), 1.73 (s, 1H), 1.67 (d, J=8.6, 1H), 1.49-1.31 (m, 4H). rhSyk=+++

Workup

  1. extractionextracted with ethyl acetate (3×)
  2. dry with materialdried with magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-c9072c184803478da3b0bf81c64b7cda
Source dataset
uspto-grants-2016_03
Patent number
US09290490B2

Reaction notes

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