Triethylamine → 3-(5-Fluoropyrimidin-4-yl)-2-[(1R)-1-(4-methoxyphenyl)ethyl]-3-methyl-6-(1-tetrahydropyran-2-ylpyrazol-4-yl)isoindolin-1-one

HRID 1749381Notes

Reaction equation

HRID 1749381 reaction equation
C(N(CC)CC)C.Cl[C:9]1[N:14]=[CH:13][N:12]=[C:11]([C:15]2([CH3:46])[C:23]3[C:18](=[CH:19][C:20]([C:24]4[CH:25]=[N:26][N:27]([CH:29]5[CH2:34][CH2:33][CH2:32][CH2:31][O:30]5)[CH:28]=4)=[CH:21][CH:22]=3)[C:17](=[O:35])[N:16]2[C@@H:36]([C:38]2[CH:43]=[CH:42][C:41]([O:44][CH3:45])=[CH:40][CH:39]=2)[CH3:37])[C:10]=1[F:47].[H][H]>C(OCC)(=O)C.[OH-].[OH-].[Pd+2].ClC1N=CN=C(C2(C)C3C(=CC(C4C=NN(C5CCCCO5)C=4)=CC=3)C(=O)N2[C@@H](C2C=CC(OC)=CC=2)C)C=1F>[F:47][C:10]1[C:11]([C:15]2([CH3:46])[C:23]3[C:18](=[CH:19][C:20]([C:24]4[CH:25]=[N:26][N:27]([CH:29]5[CH2:34][CH2:33][CH2:32][CH2:31][O:30]5)[CH:28]=4)=[CH:21][CH:22]=3)[C:17](=[O:35])[N:16]2[C@@H:36]([C:38]2[CH:39]=[CH:40][C:41]([O:44][CH3:45])=[CH:42][CH:43]=2)[CH3:37])=[N:12][CH:13]=[N:14][CH:9]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 904080383-(6-Chloro-5-fluoro-pyrimidin-4-yl)-2-[(1R)-1-(4-methoxyphenyl)ethyl]-3-methyl-6-(1-tetrahydropyran-2-ylpyrazol-4-yl)isoindolin-1-oneHCID 178418361HCID 178418361, compound

Product 1

HCID 904078753-(5-Fluoropyrimidin-4-yl)-2-[(1R)-1-(4-methoxyphenyl)ethyl]-3-methyl-6-(1-tetrahydropyran-2-ylpyrazol-4-yl)isoindolin-1-oneYield 102.8%

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 904080383-(6-Chloro-5-fluoro-pyrimidin-4-yl)-2-[(1R)-1-(4-methoxyphenyl)ethyl]-3-methyl-6-(1-tetrahydropyran-2-ylpyrazol-4-yl)isoindolin-1-oneCatalystHCID 8857Ethyl AcetateSolvent

Procedure

Add triethylamine (40 mL, 287 mmol) and 20% palladium hydroxide on carbon (14 g) to a solution of 3-(6-chloro-5-fluoro-pyrimidin-4-yl)-2-[(1R)-1-(4-methoxyphenyl)ethyl]-3-methyl-6-(1-tetrahydropyran-2-ylpyrazol-4-yl)isoindolin-1-one (80 g, 142 mmol) in ethyl acetate (2.1 L) and hydrogenate with hydrogen gas (30 psi) at 20-25° C. for 16 hours. Repeat reaction conditions with 5 grams 3-(6-chloro-5-fluoro-pyrimidin-4-yl)-2-[(1R)-1-(4-methoxyphenyl)ethyl]-3-methyl-6-(1-tetrahydropyran-2-ylpyrazol-4-yl)isoindolin-1-one. Combine both reactions and filter through diatomaceous earth and evaporate to give the title compound as a yellow foam (77 g, 102%). ES/MS m/z: 528 (M+H).

Workup

  1. filtrationCombine both reactions and filter through diatomaceous earth
  2. customevaporate

Sources & evidence

ORD record
ord-415c9db019004159ad7c959136d0a14f
Source dataset
uspto-grants-2015_10
Patent number
US09156824B2

Reaction notes

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