Potassium Phosphate, Tribasic → tert-butyl 4-(2-(6-(N-(pyrimidin-4-yl)sulfamoyl)naphthalen-1-yl)-5-(trifluoromethyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 1473312Notes

Reaction equation

HRID 1473312 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[C:12]1[CH:21]=[CH:20][CH:19]=[C:18]2[C:13]=1[CH:14]=[CH:15][C:16]([S:22]([NH:25][C:26]1[CH:31]=[CH:30][N:29]=[CH:28][N:27]=1)(=[O:24])=[O:23])=[CH:17]2.CC1(C)C(C)(C)OB([C:40]2[CH2:45][CH2:44][N:43]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH2:42][CH:41]=2)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(C1C(C(C)(C)C)=C([Pd]Cl)C=CC=1NC)(C)(C)C.CCOC(C)=O>[N:29]1[CH:30]=[CH:31][C:26]([NH:25][S:22]([C:16]2[CH:17]=[C:18]3[C:13](=[CH:14][CH:15]=2)[C:12]([C:3]2[CH:4]=[CH:5][C:6]([C:8]([F:9])([F:10])[F:11])=[CH:7][C:2]=2[C:40]2[CH2:45][CH2:44][N:43]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH2:42][CH:41]=2)=[CH:21][CH:20]=[CH:19]3)(=[O:24])=[O:23])=[N:27][CH:28]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 866873685-(2-chloro-4-(trifluoromethyl)phenyl)-N-(pyrimidin-4-yl)naphthalene-2-sulfonamide2×

Product 1

HCID 86687369tert-butyl 4-(2-(6-(N-(pyrimidin-4-yl)sulfamoyl)naphthalen-1-yl)-5-(trifluoromethyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylateYield 46.1%

Reagents, catalysts & solvents 2

HCID 178482226HCID 178482226, compoundCatalystHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
110 °C

Procedure

A microwave vial was charged with 5-(2-chloro-4-(trifluoromethyl)phenyl)-N-(pyrimidin-4-yl)naphthalene-2-sulfonamide (Intermediate X) (82.5 mg, 0.178 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (110 mg, 0.356 mmol), potassium phosphate (113 mg, 0.534 mmol), and 1,1-bis[(di-t-butyl-p-methylaminophenyl]palladium(II) chloride (12.59 mg, 0.018 mmol). The vial was sealed, flushed with N2 and dioxane (1334 μl) and water (445 μl) was added. The mixture was sparged for 5 min with N2. The mixture was heated in a microwave at 110° C. for 4 h. The mixture was concentrated for purification by MPLC. The residue was taken up in minimal CH2Cl2 and absorbed onto a 5 g loading cartridge and passed through a silica gel column (12 g) using a 98:2 Heptane:EtOAc to 100% EtOAc (with 1% constant EtOH additive) gradient to afford tert-butyl 4-(2-(6-(N-(pyrimidin-4-yl)sulfamoyl)naphthalen-1-yl)-5-(trifluoromethyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate (50.0 mg, 0.082 mmol) as a light-yellow amorphous solid.

Workup

  1. customThe vial was sealed
  2. customflushed with N2 and dioxane (1334 μl) and water (445 μl)
  3. additionwas added
  4. customThe mixture was sparged for 5 min with N2
  5. concentrationThe mixture was concentrated for purification by MPLC
  6. customabsorbed onto a 5 g loading cartridge

Sources & evidence

ORD record
ord-7e3ab92c6089437a8ac4fa7bf46cf563
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

Loading…