Dichloromethane → HCID 90310748, compound

HRID 1519167Notes

Reaction equation

HRID 1519167 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([O:8][C:9]2[C:10]([F:26])=[C:11]([C:19]3[N:20]=[CH:21][C:22]([NH2:25])=[N:23][CH:24]=3)[CH:12]=[CH:13][C:14]=2[CH:15]2[CH2:18][CH2:17][CH2:16]2)=[N:6][CH:7]=1.CC1(C)C(C)(C)OB([C:35]2[CH:36]=[N:37][C:38]([NH2:41])=[N:39][CH:40]=2)O1.C([O-])([O-])=O.[Na+].[Na+].C(Cl)Cl>O.O1CCOCC1>[NH2:25][C:22]1[N:23]=[CH:24][C:19]([C:11]2[C:10]([F:26])=[C:9]([C:14]([CH:15]3[CH2:18][CH2:17][CH2:16]3)=[CH:13][CH:12]=2)[O:8][C:5]2[N:4]=[CH:3][C:2]([C:35]3[CH:36]=[N:37][C:38]([NH2:41])=[N:39][CH:40]=3)=[CH:7][N:6]=2)=[N:20][CH:21]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 177502122-Aminopyrimidine-5-boronic acid, pinacol esterHCID 90310726HCID 90310726, compound

Product 1

HCID 90310748HCID 90310748, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

5-(3-((5-Bromopyrimidin-2-yl)oxy)-4-cyclobutyl-2-fluorophenyl)pyrazin-2-amine (60 mg, 0.14 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine (32 mg, 0.14 mmol) were added to a sealable microwave vial equipped with a stir-bar. 1,4-Dioxane (0.58 mL) and Na2CO3 (2 M, 0.14 mL) were added And the mixture sparged with Ar for 10 min before adding Pd(dppf)Cl2.CH2Cl2 (5 mg, 0.007 mmol) and heating the reaction mixture at 80° Celsius for 15 hours. The reaction was then cooled to rt, diluted with water (5 mL), and extracted with ethyl acetate (3×10 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated to dryness. The crude product was purified by HPLC to give the title compound. MS (ESI): mass calcd. for C22H19FN8O, 430.17; m/z found, 431.1 [M+H]+. 1H NMR (500 MHz, CD3OD) δ 8.83 (s, 2H), 8.67 (s, 2H), 8.23 (s, 1H), 8.16 (s, 1H), 7.82-7.74 (m, 1H), 7.30 (d, J=8.3, 1H), 3.68 (p, J=8.9, 1H), 2.31-2.08 (m, 4H), 2.07-1.92 (m, 1H), 1.92-1.76 (m, 1H).

Workup

  1. customvial equipped with a stir-bar
  2. customthe mixture sparged with Ar for 10 min
  3. additionbefore adding Pd(dppf)Cl2
  4. extractionextracted with ethyl acetate (3×10 mL)
  5. dry with materialThe combined organic extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customThe crude product was purified by HPLC

Sources & evidence

ORD record
ord-ab5c3207895049b389c4ed07a1cd5b9c
Source dataset
uspto-grants-2015_07
Patent number
US09073876B2

Reaction notes

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