1-Hydroxybenzotriazole → HCID 67058475, compound

HRID 1919487Notes

Reaction equation

HRID 1919487 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].[CH3:23][CH2:24][N:25](C(C)C)[CH:26](C)[CH3:27].C1C=C[C:35]2[N:40](O)N=[N:38][C:36]=2C=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[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:25]1[CH2:26][CH2:27][N:40]2[CH:35]=[CH:36][N:38]=[C:23]2[CH2:24]1)=[O:12])=[O:6])[CH3:3]

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11347588(R)-b-(Boc-amino)-2,5-difluorobenzenebutanoic acid2×

Product 1

HCID 67058475HCID 67058475, compoundYield 64.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The title compound was prepared from 2-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-c]pyrazine (277 mg, 1.45 mmol, from Example 1, Step B), (3R)-3-[(1,1-dimethylethoxycarbonyl)amino]-4-(2,5-difluorophenyl)butanoic acid (Intermediate 1, 416 mg, 1.32 mmol), DIPEA (226 mg, 1.58 mol), HOBT (216 mg, 1.98 mol) and HATU (753 mg, 1.98 mol) in DMF (6 mL), using a procedure analogous to that described in Example 1 Step C, except for the purification method. The compound was purified by preparative TLC (silica gel, 20% hexane in ethyl acetate, then 10% methanol in dichloromethane) to give 360 mg of the title compound as a foamy solid. 1H NMR (500 MHz, CDCl3) δ 1.35 (s, 9H), 2.62 (m, 2H), 2.88 (m, 2H) 3.88-4.16 (m, 5H), 4.73 (s, 1H), 4.85 (m, 1H) 5.26-5.39 (m, 1H) 6.90 (bs, 1H), 7.06 (m, 2H), 7.24 (m, 1H). ESI-MS 489 (M+1).

Workup

  1. customthat described in Example 1 Step C, except for the purification method
  2. customThe compound was purified by preparative TLC (silica gel, 20% hexane in ethyl acetate

Sources & evidence

ORD record
ord-3425487529eb4a3fa64397f361a7d97e
Source dataset
uspto-grants-2012_05
Patent number
US08168637B2

Reaction notes

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