1-Hydroxybenzotriazole → HCID 67058475, compound

HRID 2091719Notes

Reaction equation

HRID 2091719 reaction equation
FC(F)(F)[C:3]1[N:4]=[C:5]2[CH2:10][NH:9][CH2:8][CH2:7][N:6]2[CH:11]=1.[CH3:14][C:15]([CH3:35])([O:17][C:18]([NH:20][C@H:21]([CH2:26][C:27]1[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:28]=1[F:34])[CH2:22][C:23](O)=[O:24])=[O:19])[CH3:16].CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH3:16][C:15]([CH3:35])([O:17][C:18]([NH:20][C@H:21]([CH2:26][C:27]1[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:28]=1[F:34])[CH2:22][C:23]([N:9]1[CH2:8][CH2:7][N:6]2[CH:11]=[CH:3][N:4]=[C:5]2[CH2:10]1)=[O:24])=[O:19])[CH3:14]

Participants

7

Reactant 5

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×HCID 147199282-(trifluoromethyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazine

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-a]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-224bd3ac94544bd38e992b05f9f328b0
Source dataset
uspto-grants-2013_05
Patent number
US08440668B2

Reaction notes

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