HCID 67271598, compound → HCID 58851545, compound

HRID 1696546Notes

Reaction equation

HRID 1696546 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[C:15]=2[Cl:21])=[O:12])[N:7]([C:22]2[CH:31]=[C:30]3[C:25]([CH2:26][C@@H:27]([C:39](=[O:41])[NH2:40])[N:28](C(OC(C)(C)C)=O)[CH2:29]3)=[CH:24][CH:23]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2]>Cl.O1CCOCC1>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[C:15]=2[Cl:21])=[O:12])[N:7]([C:22]2[CH:31]=[C:30]3[C:25]([CH2:26][C@@H:27]([C:39](=[O:41])[NH2:40])[NH:28][CH2:29]3)=[CH:24][CH:23]=2)[N:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 1

HCID 67271598HCID 67271598, compound

Product 1

HCID 58851545HCID 58851545, compoundYield 92.6%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of (3S)-2-t-butyl 3-methyl 7-(3-t-butyl-5-(3-(2,3-dichlorophenyl)ureido)-1H-pyrazol-1-yl)-3,4-dihydroiso-quinoline-2,3 (1H)-dicarboxylate (from Example 177, 0.100 g, 0.163 mmol) in 7N NH3/MeOH (3 mL) was stirred at RT overnight. The solvent was removed under reduced pressureand the residue was dissolved in CH2Cl2 (2 mL). Boc anhydride (0.036 g, 0.163 mmol) was added and the solution was stirred at room temperature for 30 min. The solvent was evaporated and the residue was purified by column chromatography to yield (3S)-t-butyl 7-(3-t-butyl-5-(3-(2,3-dichlorophenyl)ureido)-1 H-pyrazol-1-yl)-3-carbamoyl-3,4-dihydroisoquinoline-2(1H)-carboxylate (85 mg, 87% yield) as a white solid. 1H-NMR (400 MHz, acetone-d6): δ 8.66 (brs, 1H), 8.27 (dd, J=8.4, and 2.0 Hz, 1H), 8.21 (brs, 1H), 7.42-7.37 (m, 2H), 7.35-7.29 (m, 2H), 7.24 (dd, J=8.0, and 1.6 Hz, 1H), 6.88 (brs, 1H), 6.49 (s, 1H), 6.33 (brs, 1H), 4.97-4.45 (m, 3H), 3.36-3.09 (m, 2H), 1.47-1.45 (m, 9H), 1.32 (s, 9H); MS (ESI) m/z: 601.2 (M+H+). (3S)-t-butyl 7-(3-t-butyl-5-(3-(2,3-dichlorophenyl)ureido)-1H-pyrazol-1-yl)-3-carbamoyl-3,4-dihydroisoquinoline-2(1H)-carboxylate (0.085 g, 0.14 mmol) was dissolved in 4N HCl in dioxane (5 mL) and the solution was stirred at RT for 30 min. The solvent was removed under reduced pressureand the residue was dissolved in H2O/MeCN (1:1) and lyophilized to yield 1-(3-t-butyl-1-((3S)-3-carbamoyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-1 H-pyrazol-5-yl)-3-(2,3-dichlorophenyl)urea (65 mg, 85% yield) as a white solid. 1H-NMR (CD3OD) shows rotameric mixture. MS (ESI) m/z: 501.2 (M+H+).

Workup

  1. customThe solvent was removed
  2. dissolutionwas dissolved in H2O/MeCN (1:1)

Sources & evidence

ORD record
ord-941fd99d2ed045f6a8f219c546504d09
Source dataset
uspto-grants-2012_04
Patent number
US08163756B2

Reaction notes

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