Sodium Carbonate → (S)-6-(2-(2-(trifluoromethyl)pyrrolidin-1-yl)pyrimidin-5-yl)pyridine-2-amine

HRID 1054480Notes

Reaction equation

HRID 1054480 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[N:11][C:12]([N:15]3[CH2:19][CH2:18][CH2:17][C@H:16]3[C:20]([F:23])([F:22])[F:21])=[N:13][CH:14]=2)O1.Br[C:26]1[N:31]=[C:30]([NH2:32])[CH:29]=[CH:28][CH:27]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[F:23][C:20]([F:21])([F:22])[C@@H:16]1[CH2:17][CH2:18][CH2:19][N:15]1[C:12]1[N:13]=[CH:14][C:9]([C:26]2[N:31]=[C:30]([NH2:32])[CH:29]=[CH:28][CH:27]=2)=[CH:10][N:11]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 3008092-Amino-6-bromopyridineHCID 86727118(S)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(2-(trifluoromethyl)pyrrolidin-1-yl)pyrimidine2×

Product 1

HCID 86727117(S)-6-(2-(2-(trifluoromethyl)pyrrolidin-1-yl)pyrimidin-5-yl)pyridine-2-amineYield 83.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A flask was charged with (S)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(2-(trifluoromethyl)pyrrolidin-1-yl)pyrimidine (Intermediate 2, 5 g, 14.57 mmol), 6-bromopyridin-2-amine (3.03 g, 17.48 mmol), Pd(PPh3)4 (1.684 g, 1.457 mmol) and 1,4-dioxane (36 mL). The reaction mixture was purged with nitrogen for several minutes before aqueous 2M sodium carbonate (14.57 mL, 29.1 mmol) solution was added. The reaction mixture was then purged with nitrogen for another 10 minutes at 25° C. before it was heated to 90° C. under nitrogen overnight. 1,4-Dioxane was removed in vacuo and the crude mixture was diluted with EtOAc. The product was washed with water (3×) and brine. The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was purified on silica gel chromatography eluting with MeOH:CH2Cl2 (2:98) to yield 3.75 g (12.13 mmol, 83%) of the title product as an off white solid; 1H NMR (300 MHz, DMSO-d6) δ 8.99 (s, 2H), 7.44 (dd, J=8.1, 7.5 Hz, 1H), 7.13-6.93 (m, 1H), 6.47-6.34 (m, 1H), 6.04 (s, 2H), 5.22-4.90 (m, 1H), 3.67 (t, J=6.1 Hz, 2H), 2.32-1.95 (m, 4H); m/z found [M+H]+=310.45.

Workup

  1. additionwas added
  2. customThe reaction mixture was then purged with nitrogen for another 10 minutes at 25° C. before it
  3. custom1,4-Dioxane was removed in vacuo
  4. additionthe crude mixture was diluted with EtOAc
  5. washThe product was washed with water (3×) and brine
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude material was purified on silica gel chromatography
  10. washeluting with MeOH:CH2Cl2 (2:98)

Sources & evidence

ORD record
ord-2afe5645931543148433ba52ee0c7505
Source dataset
uspto-grants-2016_07
Patent number
US09394308B2

Reaction notes

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