1,2-Dichloroethane → Methyl (2r)-3-[(4-{[(4-tert-butylcyclohexyl)(1-methyl-1h-benzimidazol-2-yl)amino]-methyl}benzoyl)amino]-2-hydroxypropanoate

HRID 229990노트

반응식

HRID 229990 반응식
[C:1]([CH:5]1[CH2:10][CH2:9][CH:8]([N:11]([CH2:22][C:23]2[CH:31]=[CH:30][C:26]([C:27](O)=[O:28])=[CH:25][CH:24]=2)[C:12]2[N:16]([CH3:17])[C:15]3[CH:18]=[CH:19][CH:20]=[CH:21][C:14]=3[N:13]=2)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[CH3:32][O:33][C:34](=[O:39])[CH:35]([OH:38])[CH2:36][NH2:37].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C>CN(C=O)C>[C:1]([CH:5]1[CH2:6][CH2:7][CH:8]([N:11]([CH2:22][C:23]2[CH:24]=[CH:25][C:26]([C:27]([NH:37][CH2:36][C@@H:35]([OH:38])[C:34]([O:33][CH3:32])=[O:39])=[O:28])=[CH:30][CH:31]=2)[C:12]2[N:16]([CH3:17])[C:15]3[CH:18]=[CH:19][CH:20]=[CH:21][C:14]=3[N:13]=2)[CH2:9][CH2:10]1)([CH3:4])([CH3:2])[CH3:3]

참가 물질

7

반응물 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 11105589Methyl 3-amino-2-hydroxypropanoateHCID 688367154-{[(4-tert-Butylcyclohexyl)(1-methyl-1H-benzimidazol-2-yl)amino]methyl}-benzoic acid

생성물 1

HCID 57758784Methyl (2r)-3-[(4-{[(4-tert-butylcyclohexyl)(1-methyl-1h-benzimidazol-2-yl)amino]-methyl}benzoyl)amino]-2-hydroxypropanoate

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of the title compound of Example 5 Step A (0.32 mmol, 145 mg), the hydrochloride salt of 2-hydroxy β-alanine methyl ester (0.48 mmol, 74 mg), HOBt (0.8 mmol, 121 mg) and EDC (0.96 mmol, 183 mg) in 2 mL of DMF was added DIEA (1.6 mmol, 0.28 mL). After 3 h the reaction was partitioned into EtOAc/brine. The organic phase was dried with MgSO4 and concentrated under reduced pressure. The product was purified by flash chromatography on silica eluting with 1:25:74 MeOH/EtOAc/DCM, affording the title compound as a foamy solid. 1HNMR (500 MHz, DMSO-d6): δ 8.47 (t, 1H), 7.75 (d, 2H), 7.60 (m, 1H), 7.48 (m, 1H), 7.45 (d, 2H), 7.30-7.37 (overlapping m, 2H), 4.80 (s, 2H), 3.76 (s, 3H), 3.70 (m, 1H), 3.60 (s, 3H), 3.50 (m, 1H), 3.39 (m, 1H), 2.02 (m, 2H), 1.82 (m, 2H), 1.71 (m, 2H), 1.18 (m, 2H), 1.03 (m, 1H), 0.85 (s, 9H). MS (ESI): m/z 521 (M+H). HPLC A: 1.94 min.

후처리

  1. customAfter 3 h the reaction was partitioned into EtOAc/brine
  2. dry with materialThe organic phase was dried with MgSO4
  3. concentrationconcentrated under reduced pressure
  4. customThe product was purified by flash chromatography on silica eluting with 1:25:74 MeOH/EtOAc/DCM

출처 및 근거

ORD 기록
ord-7efb78a9e5bd48df9338056dbeebced7
출처 데이터셋
uspto-grants-2009_07
특허 번호
US07563815B2

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