Triethylamine → HCID 68228670, compound

HRID 2370342Notes

Reaction equation

HRID 2370342 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:5]=[CH:6][C:7]([F:37])=[C:8]([CH:10]2[CH2:15][CH2:14][N:13]([C:16]([C:18]3[C:26]4[C:21](=[C:22]([F:32])[CH:23]=[CH:24][C:25]=4[O:27][C:28]([F:31])([F:30])[F:29])[N:20]([CH2:33][CH2:34][O:35][CH3:36])[CH:19]=3)=[O:17])[CH2:12][CH2:11]2)[CH:9]=1.[NH:38]([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[C@H:39]([C:43]([NH:45][CH2:46][C:47](O)=[O:48])=[O:44])[CH:40]([CH3:42])[CH3:41].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(CC)CC>CN(C=O)C.CCOC(C)=O>[C:53]([O:52][C:50](=[O:51])[NH:38][C@H:39]([C:43](=[O:44])[NH:45][CH2:46][C:47](=[O:48])[NH:2][CH2:3][C:4]1[CH:5]=[CH:6][C:7]([F:37])=[C:8]([CH:10]2[CH2:15][CH2:14][N:13]([C:16]([C:18]3[C:26]4[C:21](=[C:22]([F:32])[CH:23]=[CH:24][C:25]=4[O:27][C:28]([F:31])([F:29])[F:30])[N:20]([CH2:33][CH2:34][O:35][CH3:36])[CH:19]=3)=[O:17])[CH2:12][CH2:11]2)[CH:9]=1)[CH:40]([CH3:41])[CH3:42])([CH3:54])([CH3:56])[CH3:55]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 7014901BOC-VAL-GLY-OHHCID 87328684HCID 87328684, compound

Product 1

HCID 68228670HCID 68228670, compoundYield 95%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of [4-(5-aminomethyl-2-fluoro-phenyl)-piperidin-1-yl]-[7-fluoro-1-(2-methoxy-ethyl)-4-trifluoromethoxy-1H-indol-3-yl]-methanone hydrochloride (0.3 g, 0.55 mmol), BOC-Val-GlyOH (0.18 g, 0.66 mmol), EDCI (0.126 g, 0.66 mmol), HOBT (0.224 g, 1.65 mmol), and Et3N (0.23 ml, 1.65 mmol) in DMF (15 mL) was stirred at room temperature overnight. The reaction mixture was poured into EtOAc and the organic layer washed with water and brine. The organic layer was dried over MgSO4, filtered and concentrated in vacuo to give the crude product. Purification by flash chromatography on SiO2 eluting with 3% MeOH/CH2Cl2 provided the desired product (0.4 g, 95%). 1H NMR (300 MHz, CDCl3) δ 7.4 (s, 1H), 7.1 (m, 2H), 7.0-6.8 (m, 3H), 6.7 (bs, 1H), 5.1 (bs, 1H), 4.5-4.3 (m, 4H), 4.1-3.7 (m, 6H), 3.35 (s, 3H), 3.1 (m, 3H), 2.1 (m, 1H), 1.8-1.6 (m, 6H), 1.4 (s, 9H), 0.9 (m, 6H). MS m/z: [M+H]+=768.

Workup

  1. washthe organic layer washed with water and brine
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto give the crude product
  6. customPurification by flash chromatography on SiO2 eluting with 3% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-90c331f5bf544b8d937aa05bacdb50c8
Source dataset
uspto-grants-2014_04
Patent number
US08710080B2

Reaction notes

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