Dichloromethane → Methyl 3-{[(4-{3-[1-(tert-butoxycarbonyl)-4-piperidinyl]anilino}-4-oxobutyl)amino]carbonyl}-4-(4-fluorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate

HRID 1452658Notes

Reaction equation

HRID 1452658 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[N:13]([C:14]([NH:16][CH2:17][CH2:18][CH2:19][C:20](O)=[O:21])=[O:15])[C:12](=[O:23])[NH:11][C:10]([CH3:24])=[C:9]2[C:25]([O:27][CH3:28])=[O:26])=[CH:4][CH:3]=1.[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(C)C1C=CN=CC=1.CN(C=O)C.O>[C:29]([O:33][C:34]([N:36]1[CH2:41][CH2:40][CH:39]([C:42]2[CH:43]=[C:44]([CH:45]=[CH:46][CH:47]=2)[NH:48][C:20](=[O:21])[CH2:19][CH2:18][CH2:17][NH:16][C:14]([N:13]2[CH:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)[C:9]([C:25]([O:27][CH3:28])=[O:26])=[C:10]([CH3:24])[NH:11][C:12]2=[O:23])=[O:15])[CH2:38][CH2:37]1)=[O:35])([CH3:32])([CH3:30])[CH3:31]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22049268tert-Butyl 4-(3-aminophenyl)piperidine-1-carboxylateHCID 575269344-{[(6-(4-Fluorophenyl)-5-(methoxycarbonyl)-4-methyl-2-oxo-3,6-dihydro-1(2H)-pyrimidinyl)carbonyl]amino}butanoic acid

Product 1

HCID 57526947Methyl 3-{[(4-{3-[1-(tert-butoxycarbonyl)-4-piperidinyl]anilino}-4-oxobutyl)amino]carbonyl}-4-(4-fluorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-5-pyrimidinecarboxylateYield 33.2%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A 10-mL RB-flask was charged with 4-{[(6-(4-fluorophenyl)-5-(methoxycarbonyl)-4-methyl-2-oxo-3,6-dihydro-1(2H)-pyrimidinyl)carbonyl]amino}butanoic acid (77.0 mg, 0.189 mmol), tert-butyl-4-[3-(amino)phenyl]-1-piperidinecarboxylate (52.2 mg, 0.189 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodimide hydrochloride (0.567 mmol, 87.8 mg), 4-dimethylaminopyridine (11.5 mg, 0.0945 mmol) in DMF:DCM (0.2:2.0 mL) at room temperature. The reaction mixture was stirred for 12 h and water (10.0 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 (40.9 mg, 33.2%): 1H NMR (400 MHz, CDCl3) δ 8.03 (m, 3H), 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: 652.2 (M+H)+.

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-fadf103c9ce641989d13db880541104e
Source dataset
uspto-grants-2009_01
Patent number
US07473698B2

Reaction notes

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