(S)-2-benzyl 3-ethyl 8-(2-amino-6-((R)-2,2,2-trifluoro-1-(3'-(hydroxymethyl)-4'-methyl-3-(3-methyl-1H-pyrazol-1-yl)-[1,1'-biphenyl]-4-yl)ethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate → (S)-ethyl 8-(2-amino-6-((R)-2,2,2-trifluoro-1-(3'-(hydroxymethyl)-4'-methyl-3-(3-methyl-1H-pyrazol-1-yl)-[1,1'-biphenyl]-4-yl)ethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylate

HRID 1499139Notes

Reaction equation

HRID 1499139 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:32][CH2:31][C:11]3([CH2:15][N:14](C(OCC4C=CC=CC=4)=O)[C@H:13]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:12]3)[CH2:10][CH2:9]2)[CH:5]=[C:4]([O:33][C@H:34]([C:39]2[CH:44]=[CH:43][C:42]([C:45]3[CH:50]=[CH:49][C:48]([CH3:51])=[C:47]([CH2:52][OH:53])[CH:46]=3)=[CH:41][C:40]=2[N:54]2[CH:58]=[CH:57][C:56]([CH3:59])=[N:55]2)[C:35]([F:38])([F:37])[F:36])[N:3]=1>CCOC(C)=O.[Pd]>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:32][CH2:31][C:11]3([CH2:15][NH:14][C@H:13]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:12]3)[CH2:10][CH2:9]2)[CH:5]=[C:4]([O:33][C@H:34]([C:39]2[CH:44]=[CH:43][C:42]([C:45]3[CH:50]=[CH:49][C:48]([CH3:51])=[C:47]([CH2:52][OH:53])[CH:46]=3)=[CH:41][C:40]=2[N:54]2[CH:58]=[CH:57][C:56]([CH3:59])=[N:55]2)[C:35]([F:38])([F:37])[F:36])[N:3]=1

Participants

4

Reactant 1

HCID 117952255(S)-2-benzyl 3-ethyl 8-(2-amino-6-((R)-2,2,2-trifluoro-1-(3'-(hydroxymethyl)-4'-methyl-3-(3-methyl-1H-pyrazol-1-yl)-[1,1'-biphenyl]-4-yl)ethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate

Product 1

HCID 117947819(S)-ethyl 8-(2-amino-6-((R)-2,2,2-trifluoro-1-(3'-(hydroxymethyl)-4'-methyl-3-(3-methyl-1H-pyrazol-1-yl)-[1,1'-biphenyl]-4-yl)ethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylate

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (S)-2-benzyl 3-ethyl 8-(2-amino-6-((R)-2,2,2-trifluoro-1-(3′-(hydroxymethyl)-4′-methyl-3-(3-methyl-1H-pyrazol-1-yl)-[1,1′-biphenyl]-4-yl)ethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate (200 mg, 0.24 mmol) in EtOAc (5 mL) was hydrogenated using an H-Cube apparatus and a 10% (w/w) Pd/C cartridge with a flow rate of 1.0 mL/min at RT. Purification on normal phase silica gel (EtOAc/heptane) provided (S)-ethyl 8-(2-amino-6-((R)-2,2,2-trifluoro-1-(3′-(hydroxymethyl)-4′-methyl-3-(3-methyl-1H-pyrazol-1-yl)-[1,1′-biphenyl]-4-yl)ethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylate.

Workup

  1. customat RT
  2. customPurification on normal phase silica gel (EtOAc/heptane)

Sources & evidence

ORD record
ord-36a58ccec6d845f4a54a9f0d3ef1cff4
Source dataset
uspto-grants-2015_12
Patent number
US09199994B2

Reaction notes

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