Acetic Acid → HCID 86658256, compound

HRID 1040160Notes

Reaction equation

HRID 1040160 reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([C:20]2[S:24][C:23]([C@@:25]3([OH:37])[CH2:30][CH2:29][C@H:28]([C:31]([O:33][CH3:34])=[O:32])[C:27]([CH3:36])([CH3:35])[CH2:26]3)=[N:22][CH:21]=2)[CH:6]=[C:7]([NH:9][C:10]2[N:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][N:11]=2)[CH:8]=1.[O-:38][C:39]#[N:40].[K+].C(O)(=O)C.O>C1COCC1>[C:39]([NH:1][CH2:2][C:3]1[CH:4]=[C:5]([C:20]2[S:24][C:23]([C@@:25]3([OH:37])[CH2:30][CH2:29][C@H:28]([C:31]([OH:33])=[O:32])[C:27]([CH3:35])([CH3:36])[CH2:26]3)=[N:22][CH:21]=2)[CH:6]=[C:7]([NH:9][C:10]2[N:15]=[C:14]([C:16]([F:17])([F:19])[F:18])[CH:13]=[CH:12][N:11]=2)[CH:8]=1)(=[O:38])[NH2:40].[C:39]([NH:1][CH2:2][C:3]1[CH:4]=[C:5]([C:20]2[S:24][C:23]([C@@:25]3([OH:37])[CH2:30][CH2:29][C@H:28]([C:31]([O:33][CH3:34])=[O:32])[C:27]([CH3:35])([CH3:36])[CH2:26]3)=[N:22][CH:21]=2)[CH:6]=[C:7]([NH:9][C:10]2[N:15]=[C:14]([C:16]([F:18])([F:19])[F:17])[CH:13]=[CH:12][N:11]=2)[CH:8]=1)(=[O:38])[NH2:40]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 962WaterHCID 11378442Potassium cyanateHCID 67432750HCID 67432750, compound

Product 2

HCID 67430374HCID 67430374, compoundHCID 86658256HCID 86658256, compoundYield 184.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of methyl(1S,4R)-4-{5-[3-(aminomethyl)-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl]-1,3-thiazol-2-yl}-4-hydroxy-2,2-dimethylcyclohexanecarboxylate (40 mg, 0.075 mmol) in anhydrous THF (1.5 ml) was added potassium cyanate (12.12 mg, 0.149 mmol, 2.0 equiv), acetic acid (8.55 μl, 0.149 mmol, 2.0 equiv), and water (4.5 ml). The mixture was stirred at 50° C. for 14 h. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with EtOAc (40 ml). The organic layer were dried over Na2SO4, filtered and concentrated to provide the desired product, methyl (1S,4R)-4-[5-(3-[(carbarnoylamino)methyl]-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-4-hydroxy-2,2-dimethylcyclohexanecarboxylate (40 mg, 88%), as an orange oil. MS ESI: [M+H]+ m/z 579.2. 1H NMR (500 MHz, DMSO) δ 10.3 (s, 1H), 8.83 (d, J=4.9 Hz, 1H), 8.03 (bs, 1H), 7.88 (s, 1H), 7.50 (s, 1H), 7.28 (d, 1H, J=4.9 Hz), 7.17 (s, 1H), 6.46 (m, 1H), 5.55 (s, 2H), 4.16 (m, 2H), 3.59 (s, 3H), 2.31 (m, 1H), 1.87-1.84 (m, 4H), 1.75-1.73 (m, 2H), 1.17 (s, 3H), 0.96 (s, 3H).

Workup

  1. customThe reaction mixture was quenched with saturated aqueous NaHCO3
  2. extractionextracted with EtOAc (40 ml)
  3. dry with materialThe organic layer were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-bf3f94020c884f3d9b6206ef0726bb2d
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

Loading…