Hydrochloric Acid → (R)-4-(1-Cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxamido)-2-ureidobutanoic acid

HRID 1481038Notes

Reaction equation

HRID 1481038 reaction equation
[NH2:1][C@H:2]([CH2:6][CH2:7][NH:8][C:9]([C:11]1[N:12]=[C:13]([C:29]#[N:30])[C:14]2[C:19]([C:20]=1[OH:21])=[CH:18][CH:17]=[C:16]([O:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH:15]=2)=[O:10])[C:3]([OH:5])=[O:4].C(N(CC)CC)C.C[Si]([N:42]=[C:43]=[O:44])(C)C.Cl>C(Cl)Cl.CCOC(C)=O.O>[C:29]([C:13]1[C:14]2[C:19](=[CH:18][CH:17]=[C:16]([O:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH:15]=2)[C:20]([OH:21])=[C:11]([C:9]([NH:8][CH2:7][CH2:6][C@@H:2]([NH:1][C:43]([NH2:42])=[O:44])[C:3]([OH:5])=[O:4])=[O:10])[N:12]=1)#[N:30]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 70696Trimethylsilyl isocyanateHCID 71736906(R)-2-Amino-4-(1-cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxamido)butanoic acid

Product 1

HCID 89812844(R)-4-(1-Cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxamido)-2-ureidobutanoic acid

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

(R)-2-Amino-4-(1-cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxamido)butanoic acid (21 mg, 0.04 mmol) in CH2Cl2 (1.5 mL) was cooled to 0° C. To the solution were added triethylamine (0.05 mL, 0.32 mmol) and (trimethylsilyl)isocyanate (0.02 mL, 0.16 mmol). After stirring for 16 hours at room temperature, H2O (15 mL) and EtOAc (15 mL) were added. To the stirred mixture was added 1 N hydrochloric acid (1 mL). The layers were separated and the aqueous layer was extracted twice with EtOAc. The combined organic layers were dried over MgSO4, concentrated, and purified by flash chromatography (0-20% MeOH/CH2Cl2 with 0.5% formic acid) to give the title compound in 5 mg. MS: (−) m/z 448.29 (M−1).

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted twice with EtOAc
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. concentrationconcentrated
  5. custompurified by flash chromatography (0-20% MeOH/CH2Cl2 with 0.5% formic acid)

Sources & evidence

ORD record
ord-98a59bceadfd49a3971ea88085af3db7
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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