3-Cyclopentylpropionyl chloride → (2S)-2-tert-butoxy-2-(2-(3-cyclopentylpropanamido)-7-(8-fluoro-5-methylchroman-6-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetic acid

HRID 1468751Notes

Reaction equation

HRID 1468751 reaction equation
[NH2:1][C:2]1[CH:32]=[C:5]2[N:6]=[C:7]([CH3:31])[C:8]([C@H:22]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[C:23]([OH:25])=[O:24])=[C:9]([C:10]3[C:11]([CH3:21])=[C:12]4[C:17](=[C:18]([F:20])[CH:19]=3)[O:16][CH2:15][CH2:14][CH2:13]4)[N:4]2[N:3]=1.NC1C=C2N=C(C)C(C(OC(C)(C)C)C(O)=O)=C(C3[C:43]([CH3:53])=[C:44]4[C:49](=[C:50](F)C=3)[O:48][CH2:47][CH2:46][CH2:45]4)N2N=1.C1(CCC(Cl)=O)CCCC1.CCN(C(C)C)C(C)C>C1COCC1>[C:27]([O:26][C@@H:22]([C:8]1[C:7]([CH3:31])=[N:6][C:5]2[N:4]([N:3]=[C:2]([NH:1][C:47](=[O:48])[CH2:46][CH2:45][CH:44]3[CH2:43][CH2:53][CH2:50][CH2:49]3)[CH:32]=2)[C:9]=1[C:10]1[C:11]([CH3:21])=[C:12]2[C:17](=[C:18]([F:20])[CH:19]=1)[O:16][CH2:15][CH2:14][CH2:13]2)[C:23]([OH:25])=[O:24])([CH3:28])([CH3:29])[CH3:30]

Participants

6

Reactant 4

HCID 660393-Cyclopentylpropionyl chlorideHCID 81531DiisopropylethylamineHCID 71730302(2S)-2-(2-amino-7-(8-fluoro-5-methylchroman-6-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetic acidHCID 781617522-(2-Amino-7-(8-fluoro-5-methylchroman-6-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetic acid

Product 1

HCID 71730303(2S)-2-tert-butoxy-2-(2-(3-cyclopentylpropanamido)-7-(8-fluoro-5-methylchroman-6-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetic acidYield 35%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2S)-2-(2-amino-7-(8-fluoro-5-methylchroman-6-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetic acid (22 mg, 0.050 mmol), 3-cyclopentylpropanoyl chloride (8.79 mg, 0.055 mmol), Hunig's Base (0.026 mL, 0.15 mmol) in THF (2 mL) was stirred at rt for 16 h. It was then concentrated in vacuo and purified by prep HPLC (TFA/MeOH), the desired fractions were combined and adjusted to pH=6 using a few drops of 1N NaOH. The residue was then acidified to pH=4 using a few drops of 1N HCl. This solution was extracted with EtOAc. The organic phase was dried over MgSO4, filtered, and concentrated in vacuo to obtain (10 mg, 35%) of (2S)-2-tert-butoxy-2-(2-(3-cyclopentylpropanamido)-7-(8-fluoro-5-methylchroman-6-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetic acid as white solid.

Workup

  1. concentrationIt was then concentrated in vacuo
  2. custompurified by prep HPLC (TFA/MeOH)
  3. extractionThis solution was extracted with EtOAc
  4. dry with materialThe organic phase was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-efb6ad2c75994449a8ff2dd6858754ee
Source dataset
uspto-grants-2015_04
Patent number
US09006235B2

Reaction notes

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