3-Amino-1,2-propanediol → HCID 58851498, compound

HRID 1696550Notes

Reaction equation

HRID 1696550 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][NH:32][CH:31]([C:37](OC)=[O:38])[CH2:30]3)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH2:41][CH2:42][CH:43]([OH:46])[CH2:44][OH:45]>Cl.CO>[OH:46][CH:43]([CH2:44][OH:45])[CH2:42][NH:41][C:37]([CH:31]1[CH2:30][C:29]2[C:34](=[CH:35][CH:36]=[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])([CH3:3])[CH3:2])=[N:6]3)[CH:28]=2)[CH2:33][NH:32]1)=[O:38]

Participants

5

Reactant 2

HCID 735613-Amino-1,2-propanediolHCID 67271984HCID 67271984, compound

Product 1

HCID 58851498HCID 58851498, compoundYield 102.6%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolvent

Procedure

Using the same method as for Example 184, a solution of methyl 6-(3-t-butyl-5-(3-(3-(pyridin-3-yloxy)phenyl)ureido)-1H-pyrazol-1-yl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate (0.017 g, 0.026 mmol, available in Example 179) in 3N HCl in MeOH (2 mL) was stirred at RT overnight. The solvent was evaporated and the residue was dissolved in MeOH (0.5 mL). 3-Amino-1,2-dihydroxypropane (0.200 g, 2.20 mmol) was added and the solution was kept at RT overnight. The mixture was directly loaded on to a reverse phase column and purified to yield 1-(1-(3-((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 (16 mg, 97% yield) as a yellow solid. 1H-NMR (MeOH-d4): δ 8.66 (s, 1H), 8.60 (d, 1H, J=−5.6 Hz), 8.23-8.20 (m, 1H), 8.05 (dd, 1H, J=8.8, 5.6 Hz), 7.57 (t, 1H, J=2.0 Hz), 7.52-7.40 (m, 4H), 7.23 (d, 1H, J=8.4 Hz), 6.89 (dd, 1H, J=7.6, 1.6 Hz), 6.54 (s, 1H), 4.56 (d, 1H, J=16.8 Hz), 4.51 (d, 1H, J=16.8 Hz), 4.29 (dd, 1H, J=12.0, 4.4 Hz), 3.78-3.72 (m, 1H), 3.54-3.45 (m, 5H), 1.36 (s, 9H), one proton is buried under the MeOH peak, urea, amide, amine and hydroxy protons not visible. MS expected 600.3 found 600.2

Workup

  1. customThe solvent was evaporated
  2. dissolutionthe residue was dissolved in MeOH (0.5 mL)
  3. custompurified

Sources & evidence

ORD record
ord-3964e195cb29411ca1ab81d17edffc31
Source dataset
uspto-grants-2012_04
Patent number
US08163756B2

Reaction notes

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