Acetic Acid → [1-amino(4-{[(R)-[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl](5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]-triazol-3-yl)methyl]amino}phenyl)methylene]carbamic acid 2-methylallyl ester

HRID 2089690

Reaction equation

HRID 2089690 reaction equation
Cl.[F:2][C:3]1[C:8]([O:9][CH2:10][CH2:11][OH:12])=[CH:7][C:6]([O:13][CH3:14])=[CH:5][C:4]=1[C@@H:15]([NH:28][C:29]1[CH:37]=[CH:36][C:32]([C:33]([NH2:35])=[NH:34])=[CH:31][CH:30]=1)[C:16]1[NH:20][C:19](=[O:21])[N:18]([C:22]2[N:27]=[CH:26][CH:25]=[CH:24][N:23]=2)[N:17]=1.C(=O)([O-])[O-].[K+].[K+].C1([O:50][C:51](=O)[O:52][CH2:53][C:54]([CH3:56])=[CH2:55])C=CC=CC=1.C(O)(=O)C>C(OCC)(=O)C.O.CS(C)=O>[CH3:56][C:54](=[CH2:55])[CH2:53][O:52][C:51](=[O:50])[N:34]=[C:33]([C:32]1[CH:31]=[CH:30][C:29]([NH:28][C@H:15]([C:4]2[CH:5]=[C:6]([O:13][CH3:14])[CH:7]=[C:8]([O:9][CH2:10][CH2:11][OH:12])[C:3]=2[F:2])[C:16]2[NH:20][C:19](=[O:21])[N:18]([C:22]3[N:23]=[CH:24][CH:25]=[CH:26][N:27]=3)[N:17]=2)=[CH:37][CH:36]=1)[NH2:35]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 11430Potassium CarbonateHCID 151790822-Methyl-allyl phenyl carbonateHCID 1363340354-{[(R)-[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl](5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]-triazol-3-yl)methyl]amino}benzamidine hydrochloride

Product 1

HCID 136334036[1-amino(4-{[(R)-[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl](5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]-triazol-3-yl)methyl]amino}phenyl)methylene]carbamic acid 2-methylallyl ester

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a mixture of 4-{[(R)-[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl](5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]-triazol-3-yl)methyl]amino}benzamidine hydrochloride (5.0 g, 9.41 mmol), potassium carbonate (2.6 g, 18.8 mmol), and dimethyl sulfoxide (15 mL), carbonic acid 2-methylallyl ester phenyl ester [CAS No. 138621-73-5] (1.57 g, 8.19 mmol) was added, and the resulting mixture was stirred at room temperature for 4 days. Ethyl acetate (100 mL) and water (200 mL) were added to the reaction solution, and the aqueous layer was collected. Acetic acid (1.62 mL, 28.2 mmol) was added dropwise to the aqueous layer with stirring, and the precipitated solid was filtered and sequentially washed with water (20 mL) and diethyl ether (20 mL). The solid obtained was suspended in ethyl acetate, filtered, and then dried under air flow. The dried solid was suspended in ethyl acetate (50 mL), and the suspension was stirred for 1 day. The suspension was filtered, and the solid obtained was washed with ethyl acetate and dried under air flow to obtain the captioned compound (4.87 g) as a yellow solid.

Workup

  1. addition138621-73-5] (1.57 g, 8.19 mmol) was added
  2. customthe aqueous layer was collected
  3. stirringwith stirring
  4. filtrationthe precipitated solid was filtered
  5. washsequentially washed with water (20 mL) and diethyl ether (20 mL)
  6. customThe solid obtained
  7. filtrationfiltered
  8. customdried under air flow
  9. stirringthe suspension was stirred for 1 day
  10. filtrationThe suspension was filtered
  11. customthe solid obtained
  12. washwas washed with ethyl acetate
  13. customdried under air flow

Sources & evidence

ORD record
ord-82751cfed9674176a7c83b1e82b227e2
Source dataset
uspto-grants-2013_05
Patent number
US08436009B2

Linked notes

Loading…