Sodium Carbonate → HCID 71285538, compound

HRID 1752419Notes

Reaction equation

HRID 1752419 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]([NH2:10])=[O:9])[CH:5]=[C:4]([N:11]([CH2:16][CH:17]2[CH2:21][O:20][C:19]([CH3:23])([CH3:22])[O:18]2)[S:12]([CH3:15])(=[O:14])=[O:13])[N:3]=1.[F:24][C:25]1[CH:46]=[CH:45][C:28]([O:29][C:30]2[CH:35]=[CH:34][C:33](B3OC(C)(C)C(C)(C)O3)=[CH:32][CH:31]=2)=[CH:27][CH:26]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:22][C:19]1([CH3:23])[O:18][CH:17]([CH2:16][N:11]([C:4]2[N:3]=[C:2]([C:33]3[CH:32]=[CH:31][C:30]([O:29][C:28]4[CH:27]=[CH:26][C:25]([F:24])=[CH:46][CH:45]=4)=[CH:35][CH:34]=3)[N:7]=[C:6]([C:8]([NH2:10])=[O:9])[CH:5]=2)[S:12]([CH3:15])(=[O:14])=[O:13])[CH2:21][O:20]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 666684382-[4-(4-Fluorophenoxy)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 89423130HCID 89423130, compound

Product 1

HCID 71285538HCID 71285538, compoundYield 80.5%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 2-chloro-6-(N-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)methylsulfonamido)pyrimidine-4-carboxamide (0.365 g, 1.00 mmol) in dioxane (5 mL) was added 2-(4-(4-fluorophenoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.379 g, 1.21 mmol), 2M aqueous Na2CO3 (1.0 mL, 2.0 mmol), and PdCl2(dppf) (0.046 g, 0.056 mmol). The reaction vessel was flushed with argon, sealed, and heated at 80° C. overnight. After cooling, the reaction mixture was evaporated in vacuo to a residue. The residue was chromatographed over silica gel with 30-80% EtOAc in hexanes. The product fractions were evaporated to a residue and triturated with 5 mL 1:1 EtOAc/hexanes. The solid was filtered off, rinsed twice with 1 mL 1:1 EtOAc/hexanes, and dried under vacuum at 40° C. to give 6-(N-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)methylsulfonamido)-2-(4-(4-fluorophenoxy)phenyl)pyrimidine-4-carboxamide as a tan-orange powder (0.416 g, 0.805 mmol, 80% yield). 1H NMR (400 MHz, DMSO-d6): 8.61-8.55 (3H, m), 8.01 (1H, s), 7.94-7.91 (1H, m), 7.33-7.26 (2H, m), 7.23-7.17 (2H, m), 7.10 (2H, d, J=9.0 Hz), 4.44-4.37 (1H, m), 4.35-4.28 (1H, m), 4.22-4.15 (1H, m), 4.07 (1H, dd, J=8.8 Hz, 6.6 Hz), 3.81 (1H, dd, J=8.6 Hz, 5.3 Hz), 3.52 (3H, s), 1.35 (3H, s), 1.23 (3H, s). LC/MS: m/z=517.2 [M+H]+.

Workup

  1. customThe reaction vessel was flushed with argon
  2. customsealed
  3. temperatureAfter cooling
  4. customthe reaction mixture was evaporated in vacuo to a residue
  5. customThe residue was chromatographed over silica gel with 30-80% EtOAc in hexanes
  6. customThe product fractions were evaporated to a residue
  7. customtriturated with 5 mL 1:1 EtOAc/hexanes
  8. filtrationThe solid was filtered off
  9. washrinsed twice with 1 mL 1:1 EtOAc/hexanes
  10. customdried under vacuum at 40° C.

Sources & evidence

ORD record
ord-bc156fb15a664cfeab202ddbfa36c540
Source dataset
uspto-grants-2015_10
Patent number
US09163008B2

Reaction notes

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