3-Amino-1,2-propanediol → HCID 58851687, compound

HRID 1696551Notes

Reaction equation

HRID 1696551 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](OCC)=[O:45])[CH2:30]3)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH2:49][CH2:50][CH:51]([OH:54])[CH2:52][OH:53]>Cl.CO>[OH:54][CH:51]([CH2:52][OH:53])[CH2:50][NH:49][C:44]([CH:31]1[C:30]2[C:29](=[CH:28][C:27]([N:7]3[C:8]([NH:10][C:11]([NH:13][C:14]4[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:21]5[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=5)[CH:15]=4)=[O:12])=[CH:9][C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])=[N:6]3)=[CH:36][CH:35]=2)[CH2:34][CH2:33][NH:32]1)=[O:45]

Participants

5

Reactant 2

HCID 735613-Amino-1,2-propanediolHCID 67272288HCID 67272288, compound

Product 1

HCID 58851687HCID 58851687, compoundYield 91%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolvent2×

Procedure

Using the same procedureas for Example 179, 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 (0.029 g, 0.044 mmol), available from experimental 184) in 3N hydrochloric acid in MeOH (10.0 mL) was stirred at RT for 1 h. The solvent was evaporated and the residue was dissolved in 3-amino-1,2-dihydroxypropane (0.200 g, 2.2 mmol) in MeOH (0.5 mL) and the solution was stirred at RT for 2 d. The solvent was evaporated and the residue was purified by reverse phase chromatography and coevaporated with THF/4N HCl to yield 1-(1-(1-((2,3-dihydroxypropyl)carbamoyl)-1,2,3,4-tetrahydroisoquinolin-6-yl)-3-t-butyl-1H-pyrazol-5-yl)-3-(3-(pyridin-3-yloxy)phenyl)urea (24 mg, 81% yield) as a pale yellow solid. 1H-NMR (MeOH-d4): δ 8.68 (d, 1H, J=3.2 Hz), 8.60 (d, 1H, J=7.6 Hz), 8.23 (ddd, 1H, J=8.8, 2.6, 1.0 Hz), 8.06 (dd, 1H, J=8.4, 1.4 Hz), 7.70 (dd, 1H, J=−9.0, 1.8 Hz), 7.58-7.54 (m, 3H), 7.42 (t, 1H, J=8.0 Hz), 7.22 (dt, 1H, J=8.4, 1.0 Hz), 6.90 (dd, 1H, J=6.8, 1.6 Hz), 6.58 (d, 1H, J=1.2 Hz), 5.29 (s, 1H), 3.84-3.63 (m, 2H), 3.63-3.51 (m, 5H), 3.30-2.87 (m, 2H), 1.37 (s, 9H), urea, amine, hydroxy and amide protons not visible. MS expected 600.3 found 600.2.

Workup

  1. customThe solvent was evaporated
  2. customThe solvent was evaporated
  3. customthe residue was purified by reverse phase chromatography

Sources & evidence

ORD record
ord-1a0421a52be54c1bb88358c1be2a78af
Source dataset
uspto-grants-2012_04
Patent number
US08163756B2

Reaction notes

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