1,2-Dichloroethane → 7-[(3R)-3-[(1,1-dimethylethoxycarbonyl)amino]-4-(3,4-difluorophenyl)butanoyl]-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine

HRID 1245375Notes

Reaction equation

HRID 1245375 reaction equation
[N:1]1[CH:2]=[CH:3][N:4]2[CH2:9][CH2:8][NH:7][CH2:6][C:5]=12.[CH3:10][C:11]([CH3:31])([O:13][C:14]([NH:16][C@H:17]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([F:29])=[C:25]([F:30])[CH:24]=1)[CH2:18][C:19](O)=[O:20])=[O:15])[CH3:12].CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>ClCCl>[CH3:12][C:11]([CH3:31])([O:13][C:14]([NH:16][C@H:17]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([F:29])=[C:25]([F:30])[CH:24]=1)[CH2:18][C:19]([N:7]1[CH2:8][CH2:9][N:4]2[CH:3]=[CH:2][N:1]=[C:5]2[CH2:6]1)=[O:20])=[O:15])[CH3:10]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 7009791(R)-3-((tert-butoxycarbonyl)amino)-4-(3,4-difluorophenyl)butanoic acidHCID 132470465,6,7,8-Tetrahydroimidazo(1,2-a)pyrazine

Product 1

HCID 670585127-[(3R)-3-[(1,1-dimethylethoxycarbonyl)amino]-4-(3,4-difluorophenyl)butanoyl]-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazineYield 70.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The title compound was prepared from 5,6,7,8-tetrahydroimidazo[1,2-α]pyrazine (31.3 mg, 0.254 mmol, from Step B), (3R)-3-[(1,1-dimethylethoxycarbonyl)amino]-4-(3,4-difluorophenyl)butanoic acid (80 mg, mmol), DIPEA (32.8 mg, 0.254 mmol), HOBT (41.2 mg, 0.305 mmol) and EDC (73 mg, 0.381 mmol) in 5 mL of dichloromethane, using a procedure analogous to that described in Example 1, Step C. Purification by HPLC (Gilson; YMC-Pack Pro C18 column, 100×20 mm I.D.; solvent gradient system from 10% acetonitrile, 90% water, and 0.1% trifluoroacetic acid to 90% acetonitrile, 10% water, and 0.1% trifluoroacetic acid) gave 75 mg of the title compound as a viscous oil. 1H NMR (500 Mz, CDCl3) δ 1.38 (s, 9H), 2.05 (bs, 1H), 2.62 (m, 2H), 2.89 (m, 2H) 3.81–4.04 (m, 5H), 4.64–4.88 (m, 2H). 5.38 (m, 1H) 6.88 (m, 2H), 7.0 5(m, 3H). ESI-MS 421 (M+1).

Workup

  1. customPurification by HPLC (Gilson; YMC-Pack Pro C18 column, 100×20 mm I.D.; solvent gradient system from 10% acetonitrile, 90% water, and 0.1% trifluoroacetic acid to 90% acetonitrile, 10% water, and 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-ce116a80727c489aaa0c2f284fd1a893
Source dataset
uspto-grants-2006_10
Patent number
US07125873B2

Reaction notes

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