HCID 67272288, compound → HCID 11853942, compound

HRID 1696554Notes

Reaction equation

HRID 1696554 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]([O:20][C:21]3[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=3)[CH:15]=2)=[O:12])[N:7]([C:27]2[CH:28]=[C:29]3[C:34](=[CH:35][CH:36]=2)[CH2:33][N:32](C(OC(C)(C)C)=O)[CH:31]([C:44]([O:46]CC)=[O:45])[CH2:30]3)[N:6]=1)([CH3:4])([CH3:3])[CH3:2]>Cl.CO>[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]([O:20][C:21]3[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=3)[CH:15]=2)=[O:12])[N:7]([C:27]2[CH:28]=[C:29]3[C:34](=[CH:35][CH:36]=2)[CH2:33][NH:32][CH:31]([C:44]([OH:46])=[O:45])[CH2:30]3)[N:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 1

HCID 67272288HCID 67272288, compound

Product 1

HCID 11853942HCID 11853942, compoundYield 100%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolvent

Procedure

A solution of 2-t-butyl 3-ethyl 6-(3-t-butyl-5-(3-(3-(pyridin-3-yloxy)phenyl)ureido)-1H-pyrazol-1-yl)-3,4-dihydroisoquinoline-2,3(1H)-dicarboxylate (available from Example 179, 0.102 g, 0.160 mmol) in 3N HCl in MeOH (5 mL) was stirred for 1 h. The solvent was evaporated. The residue was dissolved in THF (2 mL). 2N NaOH was added (2 mL) and then MeOH until homogenous. The solution was stirred at RT for 1 h. The solvents were evaporated, the residue was purified by reverse phase chromatography followed by coevaporation with THF/HCl to yield 6-(3-t-butyl-5-(3-(3-(pyridin-3-yloxy)phenyl)ureido)-1H-pyrazol-1-yl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (20 mg, 100%) as a white solid. 1H NMR (400 MHz, CD3OD): δ 8.66 (d, J=2.8 Hz, 1H), 8.59 (d, J=5.2 Hz, 1H), 8.22 (ddd, J=9.2, 2.8, and 0.8 Hz, 1H), 8.05 (dd, J=8.8, 5.6 Hz, 1H), 7.58 (t, J=2.0 Hz, 1H), 7.54-7.46 (m, 3H), 7.42 (t, J=8.2 Hz, 1H), 7.21 (d, J=8.0 Hz, 1H), 6.89 (dd, J=8.4, and 2.4 Hz, 1H), 6.57 (s, 1H), 6.59 (d, J=16.0 Hz, 1H), 4.51 (d, J=16.0 Hz, 1H), 4.49 (dd, J=11.2, and 5.2 Hz, 1H), 3.60 (dd, J=18.0, and 4.8 Hz, 1H), 1.37 (s, 9H), acid, amine and urea protons not visible, one proton is buried under the MeOH peak; MS (EI) m/z: 527.2 (M+H+).

Workup

  1. customThe solvent was evaporated
  2. dissolutionThe residue was dissolved in THF (2 mL)
  3. addition2N NaOH was added (2 mL)
  4. customThe solvents were evaporated
  5. customthe residue was purified by reverse phase chromatography

Sources & evidence

ORD record
ord-1085c606fa6442e8adefe8beeef4741c
Source dataset
uspto-grants-2012_04
Patent number
US08163756B2

Reaction notes

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