3-(Trifluoromethyl)-5,6,7,8-tetrahydro-(1,2,4)triazolo(4,3-a)pyrazine → 4-Desfluoro N-boc sitagliptin

HRID 1245380Notes

Reaction equation

HRID 1245380 reaction equation
[CH3:1][C:2]([CH3:22])([O:4][C:5]([NH:7][C@H:8]([CH2:13][C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=1[F:21])[CH2:9][C:10]([OH:12])=O)=[O:6])[CH3:3].[F:23][C:24]([F:35])([F:34])[C:25]1[N:29]2[CH2:30][CH2:31][NH:32][CH2:33][C:28]2=[N:27][N:26]=1>>[CH3:22][C:2]([CH3:1])([O:4][C:5]([NH:7][C@H:8]([CH2:13][C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=1[F:21])[CH2:9][C:10]([N:32]1[CH2:31][CH2:30][N:29]2[C:25]([C:24]([F:35])([F:23])[F:34])=[N:26][N:27]=[C:28]2[CH2:33]1)=[O:12])=[O:6])[CH3:3]

Participants

3

Reactant 2

HCID 101764893-(Trifluoromethyl)-5,6,7,8-tetrahydro-(1,2,4)triazolo(4,3-a)pyrazineHCID 11347588(R)-b-(Boc-amino)-2,5-difluorobenzenebutanoic acid2×

Product 1

HCID 114773554-Desfluoro N-boc sitagliptinYield 48.7%

Procedure

The title compound was prepared from (3R)-3-[(1,1-dimethylethoxycarbonyl)-amino](2,5-difluorophenyl)butanoic acid (Intermediate 1, 50 mg, 0.16 mmol) and 3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-α]pyrazine (30 mg, 0.16 mmol) using a procedure analogous to that described for Example 1, Step C. The crude product was purified by preparative TLC (silica gel, 100% ethyl acetate, then 10% methanol/dichloromethane (2×)) to afford the title compound (38.1 mg) as a solid. 1H NMR (500 MHz, CDCl3) δ 1.38 (s, 9H), 2.57˜3.05 (m, 4H),3.85˜4.30 (m, 5H), 4.90 (s, 1H), 4.95˜5.15 (m, 1H), 5.22˜5.40 (br, 1H), 6.86˜7.24 (m, 3). LC/MS (M+1-t-Boc) 390.

Workup

  1. customThe crude product was purified by preparative TLC (silica gel, 100% ethyl acetate

Sources & evidence

ORD record
ord-4cd60c9d814a424d9767e19ea0d915f8
Source dataset
uspto-grants-2006_10
Patent number
US07125873B2

Reaction notes

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