Sodium Carbonate → HCID 71283242, compound

HRID 1752440Notes

Reaction equation

HRID 1752440 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]([NH2:10])=[O:9])[CH:5]=[C:4]([N:11]2[CH2:15][C@H:14]([OH:16])[C@@H:13]([OH:17])[CH2:12]2)[N:3]=1.[F:18][C:19]1[CH:40]=[CH:39][C:22]([O:23][C:24]2[CH:29]=[CH:28][C:27](B3OC(C)(C)C(C)(C)O3)=[CH:26][CH:25]=2)=[CH:21][CH:20]=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]>[OH:17][C@@H:13]1[C@@H:14]([OH:16])[CH2:15][N:11]([C:4]2[N:3]=[C:2]([C:27]3[CH:26]=[CH:25][C:24]([O:23][C:22]4[CH:21]=[CH:20][C:19]([F:18])=[CH:40][CH:39]=4)=[CH:29][CH:28]=3)[N:7]=[C:6]([C:8]([NH2:10])=[O:9])[CH:5]=2)[CH2:12]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 666684382-[4-(4-Fluorophenoxy)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 89422611HCID 89422611, compound

Product 1

HCID 71283242HCID 71283242, compoundYield 74.1%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

To a mixture of 2-chloro-6-((3S,4S)-3,4-dihydroxypyrrolidin-1-yl)pyrimidine-4-carboxamide (0.261 g, 1.01 mmol) in dioxane (5 mL) was added 2-(4-(4-fluorophenoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.349 g, 1.11 mmol), 2M aqueous Na2CO3 (1.0 mL, 2.0 mmol) and PdCl2(dppf) (0.045 g, 0.055 mmol). The reaction vessel was flushed with argon, sealed, and heated at 100° C. overnight. After cooling, the reaction mixture was evaporated in vacuo and the residue chromatographed over silica gel with 50-100% acetone in hexanes. The product fractions were evaporated in vacuo and the residue triturated with acetonitrile (2 mL). The solid was filtered, rinsed with acetonitrile (1×1 mL), and dried under vacuum at 40° C. to give 6-((3S,4S)-3,4-dihydroxypyrrolidin-1-yl)-2-(4-(4-fluorophenoxy)phenyl)pyrimidine-4-carboxamide as a cream-colored powder (0.307 g, 0.748 mmol, 74% yield). 1H NMR (400 MHz, DMSO-d6): 8.55 (2H, d, J=8.6 Hz), 8.33 (1H, s), 7.79 (1H, s), 7.32-7.24 (2H, m), 7.20-7.13 (2H, m), 7.05 (2H, d, J=8.8 Hz), 6.90 (1H, s), 5.29 (1H, d, J=3.3 Hz), 5.21 (1H, d, J=3.3 Hz), 4.15-4.09 (1H, m), 4.09-4.05 (1H, m), 3.77-3.62 (3H, m), 3.35-3.30 (1H, m). LC/MS: m/z=411.1 [M+H]+.

Workup

  1. customThe reaction vessel was flushed with argon
  2. customsealed
  3. temperatureAfter cooling
  4. customthe reaction mixture was evaporated in vacuo
  5. customthe residue chromatographed over silica gel with 50-100% acetone in hexanes
  6. customThe product fractions were evaporated in vacuo
  7. customthe residue triturated with acetonitrile (2 mL)
  8. filtrationThe solid was filtered
  9. washrinsed with acetonitrile (1×1 mL)
  10. customdried under vacuum at 40° C.

Sources & evidence

ORD record
ord-13208bfbb35742a9b5e71042f2dd28ba
Source dataset
uspto-grants-2015_10
Patent number
US09163008B2

Reaction notes

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