Dimethylformamide → HCID 57526938, compound

HRID 1452660Notes

Reaction equation

HRID 1452660 reaction equation
[C:1]([C:4]1[CH:9]([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[C:12]([F:17])[CH:11]=2)[N:8]([C:18]([NH:20][CH2:21][CH2:22][CH2:23][C:24](O)=[O:25])=[O:19])[C:7](=[O:27])[NH:6][C:5]=1[CH3:28])(=[O:3])C.[C:29]([O:33][C:34]([N:36]1[CH2:41][CH2:40][CH:39]([C:42]2[CH:47]=[CH:46][CH:45]=[C:44]([NH2:48])[CH:43]=2)[CH2:38][CH2:37]1)=[O:35])([CH3:32])([CH3:31])[CH3:30].Cl.CN(C)CCCN=C=NCC.C(Cl)Cl.CN([CH:67]=[O:68])C>CN(C)C1C=CN=CC=1.O>[C:29]([O:33][C:34]([N:36]1[CH2:41][CH2:40][CH:39]([C:42]2[CH:47]=[CH:46][CH:45]=[C:44]([NH:48][C:24](=[O:25])[CH2:23][CH2:22][CH2:21][NH:20][C:18]([N:8]3[CH:9]([C:10]4[CH:15]=[CH:14][C:13]([F:16])=[C:12]([F:17])[CH:11]=4)[C:4]([C:1]([O:68][CH3:67])=[O:3])=[C:5]([CH3:28])[NH:6][C:7]3=[O:27])=[O:19])[CH:43]=2)[CH2:38][CH2:37]1)=[O:35])([CH3:32])([CH3:30])[CH3:31]

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 6344DichloromethaneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22049268tert-Butyl 4-(3-aminophenyl)piperidine-1-carboxylateHCID 68867481HCID 68867481, compound

Product 1

HCID 57526938HCID 57526938, compoundYield 67.8%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolvent

Procedure

A 50-mL RB-flask was charged with 4-{[(5-acetyl-6-(3,4-difluorophenyl)-4-methyl-2-oxo-3,6-dihydro-1(2H)-pyrimidinyl)carbonyl]amino}butanoic acid (313 mg, 0.854 mmol), tert-butyl-4-[3-(amino)phenyl]-1-piperidinecarboxylate (235 mg, 0.857 mmol), 1-[3-(Dimethylamino)propyl]-3-ethylcarbodimide hydrochloride (7.71 mmol, 265 mg), 4-dimethylaminopyridine (10.4 mg, 0.0854 mmol) in DMF:DCM (0.8:8.0 mL) at room temperature. The reaction mixture was stirred for 12 h and water (20.0 mL) was added to the reaction mixture. The organic layer was separated and the aqueous layer was extracted with CHCl3 (3×10 mL). The combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was chromatographed (silica, hexanes:EtOAc 9:1) to afford the desired product (378 mg, 67.8%): 1H NMR (400 MHz, CDCl3) δ 8.03 (m, 2H), 7.57 (s, 1H), 7.36-7.28 (m, 3H), 7.27-7.22 (m, 1H), 6.97-6.89 (m, 3H), 6.72 (s, 1H), 3.72 (s, 3H), 3.47-3.37 (m, 2H), 2.42 (s, 3H), 2.37-2.29 (m, 2H), 1.98-1.91 (m, 2H), 1.86-1.75 (m, 2H), 1.72-1.54 (m, 7H), 1.48 (s, 9H); ESMS m/e: 554.3 (M−100).

Workup

  1. customat room temperature
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with CHCl3 (3×10 mL)
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was chromatographed (silica, hexanes:EtOAc 9:1)

Sources & evidence

ORD record
ord-882a00a8ae6b4401bcb5ff4710592ac8
Source dataset
uspto-grants-2009_01
Patent number
US07473698B2

Reaction notes

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