2-(2,2-Dimethyl-5-oxo-1,3-dioxolan-4-yl)-4-methylpentanoic acid → (5S)-5-((1S)-1-{[(2R)-4-(5-fluoropyrimidin-2-yl)-2-methylpiperazin-1-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one

HRID 1677798Notes

Reaction equation

HRID 1677798 reaction equation
[CH3:1][C:2]1([CH3:16])[O:6][C@@H:5]([C@@H:7]([CH2:11][CH:12]([CH3:14])[CH3:13])[C:8]([OH:10])=O)[C:4](=[O:15])[O:3]1.[F:17][C:18]1[CH:19]=[N:20][C:21]([N:24]2[CH2:29][CH2:28][NH:27][C@H:26]([CH3:30])[CH2:25]2)=[N:22][CH:23]=1>>[F:17][C:18]1[CH:19]=[N:20][C:21]([N:24]2[CH2:29][CH2:28][N:27]([C:8]([C@H:7]([C@@H:5]3[O:6][C:2]([CH3:1])([CH3:16])[O:3][C:4]3=[O:15])[CH2:11][CH:12]([CH3:14])[CH3:13])=[O:10])[C@H:26]([CH3:30])[CH2:25]2)=[N:22][CH:23]=1

Participants

3

Reactant 2

HCID 63988602-(2,2-Dimethyl-5-oxo-1,3-dioxolan-4-yl)-4-methylpentanoic acidHCID 584880425-fluoro-2-[(3R)-3-methylpiperazin-1-yl]pyrimidine

Product 1

HCID 67331702(5S)-5-((1S)-1-{[(2R)-4-(5-fluoropyrimidin-2-yl)-2-methylpiperazin-1-yl]carbonyl}-3-methylbutyl)-2,2-dimethyl-1,3-dioxolan-4-one

Procedure

The title compound was prepared following the procedure of Example 4 (step a), but starting from (2R)-2-[(4S)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]-4-methylpentanoic acid and 5-fluoro-2-[(3R)-3-methylpiperazin-1-yl]pyrimidine. The crude was purified by chromatography on silica using a gradient of EtOAc: cHex (0/10 to 4/6). The title compound was isolated as a yellow oil (413 mg, 75%). TLC (EtOAc:cHex 3:7) Rf=0.25; 1H NMR (DMSO-d6) δ: 8.16 (s, 2H), 4.85-5.0 (m, 0.6H), 4.41-4.52 (m, 3.4H), 4.23 (m, 0.4H), 3.46-3.67 (m, 0.6H), 2.80-3.20 (m, 4H), 1.70-1.79 (m, 1H), 1.056 (m, 3H), 1.38 (s, 6H), 1.13-1.32 (m, 2H), 0.90 (m, 6H). HPLC (Condition A) Rt: 4.26 min (HPLC purity 96.1%). LC/MS: M+(ESI): 409.6.

Workup

  1. customThe title compound was prepared
  2. customThe crude was purified by chromatography on silica using a gradient of EtOAc

Sources & evidence

ORD record
ord-873e66bb834a4b14a33f280c101d7a64
Source dataset
uspto-grants-2011_08
Patent number
US08008302B2

Reaction notes

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