(R)-3-(tert-butoxycarbonylamino)-4-(2,4,5-trifluorophenyl)butanoic acid → N-Boc-sitagliptin

HRID 1919502Notes

Reaction equation

HRID 1919502 reaction equation
[CH3:1][C:2]([CH3:23])([O:4][C:5]([NH:7][C@H:8]([CH2:13][C:14]1[CH:19]=[C:18]([F:20])[C:17]([F:21])=[CH:16][C:15]=1[F:22])[CH2:9][C:10]([OH:12])=O)=[O:6])[CH3:3].[F:24][C:25]([F:36])([F:35])[C:26]1[N:30]2[CH2:31][CH2:32][NH:33][CH2:34][C:29]2=[N:28][N:27]=1>>[CH3:23][C:2]([CH3:1])([O:4][C:5]([NH:7][C@H:8]([CH2:13][C:14]1[CH:19]=[C:18]([F:20])[C:17]([F:21])=[CH:16][C:15]=1[F:22])[CH2:9][C:10]([N:33]1[CH2:32][CH2:31][N:30]2[C:26]([C:25]([F:36])([F:24])[F:35])=[N:27][N:28]=[C:29]2[CH2:34]1)=[O:12])=[O:6])[CH3:3]

Participants

3

Reactant 2

HCID 7146288(R)-3-(tert-butoxycarbonylamino)-4-(2,4,5-trifluorophenyl)butanoic acid2×HCID 101764893-(TRIFLUOROMETHYL)-5,6,7,8-TETRAHYDRO-[1,2,4]TRIAZOLO[4,3-A]PYRAZINE

Product 1

HCID 46836576N-Boc-sitagliptinYield 38.1%

Procedure

The title compound was prepared from (3R)-3-[(1,1-dimethylethoxy-carbonyl)-amino]-4-(2,4,5-trifluorophenyl)butanoic acid (Intermediate 3, 50.1 mg, 0.15 mmol) and 3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyrazine (39.2 mg, 0.20 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) to afford the title compound (29 mg) as a solid. 1H NMR (500 MHz, CDCl3) δ 1.37 (s, 9H), 2.61˜3.00 (m, 4H), 3.92˜4.30 (m, 5H), 4.93 (s, 1H), 4.95˜5.12 (m, 1H), 5.22˜5.35 (br, 1H), 6.83˜6.95 (m, 1H), 7.02˜7.12 (m, 1H). LC/MS (M+1-t-Bu) 452.

Workup

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

Sources & evidence

ORD record
ord-2c817bcb111e4b6f870546633e99687c
Source dataset
uspto-grants-2012_05
Patent number
US08168637B2

Reaction notes

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