Dimethylformamide → 5-(1-(4-cyanophenyl)-1H-pyrazol-5-yl)-N-(3-(dimethylamino)propyl)-6-methyl-2-oxo-1-(3-(trifluoromethyl)phenyl)-1,2-dihydropyridine-3-carboxamide

HRID 2089262Notes

Reaction equation

HRID 2089262 reaction equation
[CH3:1][N:2]([CH3:28])[CH2:3][CH2:4][CH2:5][NH:6][C:7]([C:9]1[C:10](=[O:27])[N:11]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:26])([F:25])[F:24])[CH:18]=2)[C:12]([CH3:16])=[C:13](I)[CH:14]=1)=[O:8].CC1(C)C(C)(C)OB([C:37]2[N:41]([C:42]3[CH:49]=[CH:48][C:45]([C:46]#[N:47])=[CH:44][CH:43]=3)[N:40]=[CH:39][CH:38]=2)O1.CN(C)C=O>[Pd](Cl)Cl.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2].O.C(O)(C)C>[C:46]([C:45]1[CH:44]=[CH:43][C:42]([N:41]2[C:37]([C:13]3[CH:14]=[C:9]([C:7]([NH:6][CH2:5][CH2:4][CH2:3][N:2]([CH3:28])[CH3:1])=[O:8])[C:10](=[O:27])[N:11]([C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:26])([F:25])[F:24])[CH:18]=4)[C:12]=3[CH3:16])=[CH:38][CH:39]=[N:40]2)=[CH:49][CH:48]=1)#[N:47]

Participants

7

Reactant 3

HCID 6228DimethylformamideHCID 58218051N-[3-(dimethylamino)propyl]-5-iodo-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxamideHCID 584327854-(5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)benzonitrile

Product 1

HCID 582180475-(1-(4-cyanophenyl)-1H-pyrazol-5-yl)-N-(3-(dimethylamino)propyl)-6-methyl-2-oxo-1-(3-(trifluoromethyl)phenyl)-1,2-dihydropyridine-3-carboxamideYield 57.3%

Reagents, catalysts & solvents 3

HCID 178454861HCID 178454861, compoundCatalystHCID 962WaterSolvent2×HCID 3776IsopropanolSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of N-[3-(dimethylamino)propyl]-5-iodo-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxamide (10 g, 19.71 mmol), 4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)benzonitrile (8.9 g, 29.55 mmol), water (0.71 g), N,N-dimethylformamide (100 mL) and diispropylethylamine (7.64 g, 59.14 mmol) was purged with nitrogen for 10 minutes. To the above mixture was charged 1,1′-bis(di-tert-butylphosphino) ferrocene palladium dichloride (“Pd-118” ex. Johnson Matthey, 642.38 mg, 985.62 moles) and the mixture heated to 40° C. for 12 h. The reaction mixture was cooled to room temperature and was added to a mixture of isopropanol (100 mL) and water (200 mL). The resulting mixture was stirred for 18 h. The precipitate was filtered, washed with water (50 mL) and dried under vacuum at 50° C. for 12 h to afford the title product as a brown solid (6.2 g, 56%); 1H NMR (400 MHz, DMSO-d6) δ 9.33 (t, J=5.77 Hz, 1 H), 8.07 (s, 1 H), 7.92-7.98 (m, 3 H), 7.91 (s, 1 H), 7.82-7.89 (m, 2 H), 7.72 (d, J=8.03 Hz, 1 H), 7.67 (d, J=8.53 Hz, 2 H), 6.73 (d, J=1.51 Hz, 1 H), 3.26 (q, J=6.86 Hz, 2 H), 2.25 (t, J=6.78 Hz, 2 H), 2.13 (s, 6 H), 1.75 (s, 3 H), 1.59 (p, J=7.03 Hz, 2 H); LCMSm/z: 549 [M+]

Workup

  1. customwas purged with nitrogen for 10 minutes
  2. temperatureThe reaction mixture was cooled to room temperature
  3. filtrationThe precipitate was filtered
  4. washwashed with water (50 mL)
  5. customdried under vacuum at 50° C. for 12 h

Sources & evidence

ORD record
ord-8423feada81941d7b6b302f5b2619c34
Source dataset
uspto-grants-2013_05
Patent number
US08436024B2

Reaction notes

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