(2R)-2-hydroxy-3,3-dimethylbutanoic acid → HCID 58760151, compound

HRID 857753Notes

Reaction equation

HRID 857753 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:17]2[CH:21]=[N:20][N:19]=[N:18]2)=[C:6]([CH:16]=1)[CH2:7][NH:8][C:9](=[O:15])[C@@H:10]1[CH2:14][CH2:13][CH2:12][NH:11]1.[OH:22][C@H:23]([C:27]([CH3:30])([CH3:29])[CH3:28])[C:24](O)=[O:25]>C(Cl)CCl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:17]2[CH:21]=[N:20][N:19]=[N:18]2)=[C:6]([CH:16]=1)[CH2:7][NH:8][C:9](=[O:15])[C@@H:10]1[CH2:14][CH2:13][CH2:12][N:11]1[C:24](=[O:25])[C@H:23]([OH:22])[C:27]([CH3:30])([CH3:29])[CH3:28]

Participants

4

Reactant 2

HCID 11344038(2R)-2-hydroxy-3,3-dimethylbutanoic acidHCID 69655818N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-L-prolinamide

Product 1

HCID 58760151HCID 58760151, compoundYield 92.1%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

The title compound was prepared from N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-L-prolinamide (hydrochloride salt, Example 26, Step B, 55 mg, 0.16mmol) and (2R)-hydroxy-3,3-dimethylbutyric acid (22 mg, 0.16 mmol) essentially according to the EDC coupling procedure described in Example 27, Step C (without the deprotection step). The mixture was stirred for 18 h at ambient temperature and was then concentrated in vacuo. The residue was purified directly by semi-preparative HPLC using a Waters Xterra RP8 column (1.9 cm×30 cm) using a 30 minute gradient of 95/5-water/MeCN to 100% MeCN with 0.1% TFA as the mobile phase at a flow rate of 20 mL/min. The product-containing fractions were concentrated in vacuo to afford the title compound as a white crystalline solid (62 mg). HPLC RT=2.86 min (Method A); LCMS m/z=421.3; 1H NMR (400 MHz, CDCl3): δ 9.15 (s, 1H), 7.62 (d, J=2.2 Hz, 1H), 7.51 (br m, 1H), 7.44 (dd, J=2.2, 8.4 Hz, 1H), 7.25 (d, J=8.6 Hz, 1H), 4.5 (dd, J=3.8, 8.6 Hz, 1H) 4.25 (d, J=5.3 Hz, 1H), 4.2 (m, 1H), 4.15 (s, 1H) 3.69 (m, 1H), 3.57 (m, 1H), 2.73 (br s, 1H), 1.8–2.1 (m, 4H), 1.0 (s, 9H)).

Workup

  1. concentrationwas then concentrated in vacuo
  2. customThe residue was purified directly by semi-preparative HPLC
  3. waitusing a 30 minute
  4. concentrationThe product-containing fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-e9dba668024746f28df6c5ace83327e0
Source dataset
uspto-grants-2006_12
Patent number
US07144899B2

Reaction notes

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