Dichloromethane → HCID 59548287, compound

HRID 1812237Notes

Reaction equation

HRID 1812237 reaction equation
[CH3:1][S:2]([N:5]1[CH2:10][CH2:9][NH:8][CH2:7][CH2:6]1)(=[O:4])=[O:3].[NH2:11][C:12]1[N:17]=[C:16]([CH3:18])[N:15]=[C:14]([C:19]2[N:24]=[C:23]([C:25](=O)[CH3:26])[CH:22]=[N:21][C:20]=2[NH:28][C:29]2[CH:30]=[N:31][C:32]([O:36][CH3:37])=[C:33]([F:35])[CH:34]=2)[CH:13]=1.C(Cl)Cl.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O1CCCC1.N.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[F:35][C:33]1[CH:34]=[C:29]([NH:28][C:20]2[C:19]([C:14]3[N:15]=[C:16]([CH3:18])[N:17]=[C:12]([NH2:11])[CH:13]=3)=[N:24][C:23]([CH:25]([N:8]3[CH2:9][CH2:10][N:5]([S:2]([CH3:1])(=[O:4])=[O:3])[CH2:6][CH2:7]3)[CH3:26])=[CH:22][N:21]=2)[CH:30]=[N:31][C:32]=1[O:36][CH3:37]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 7091611-(Methylsulfonyl)piperazineHCID 5049666Sodium triacetoxyborohydrideHCID 66600038HCID 66600038, compound

Product 1

HCID 59548287HCID 59548287, compoundYield 23%

Reagents, catalysts & solvents 3

HCID 11026Titanium isopropoxideCatalystHCID 222AmmoniaSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of 1-(methylsulfonyl)piperazine (13.34 mg, 0.081 mmol, Apollo), 1-(6-(6-amino-2-methylpyrimidin-4-yl)-5-(5-fluoro-6-methoxypyridin-3-ylamino)pyrazin-2-yl)ethanone (15 mg, 0.041 mmol) and titanium(iv) isopropoxide (0.048 mL, 0.162 mmol, Aldrich, St. Louis, Mo.) in tetrahydrofuran (0.5 mL) was stirred at 75° C. for 25 h. The mixture was cooled down to 20° C. and CH2Cl2 (1 mL) was added followed by sodium triacetoxyborohydride (34.4 mg, 0.162 mmol). The reaction mixture was stirred at room temperature for 5 h. The reaction mixture was diluted with ammonia (3 mL, 30% in water) and extracted with CH2Cl2 (2×20 mL). The combined organic extracts were washed with saturated NaCl (5 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as a yellow solid. The crude product was purified by silica gel chromatography eluting with 5% MeOH/CH2Cl2 to give 6-(3-(5-fluoro-6-methoxypyridin-3-ylamino)-6-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyrazin-2-yl)-2-methylpyrimidin-4-amine (4.8 mg, 9.27 μmol, 23% yield). 1H NMR (300 MHz, CDCl3) δ 1.44 (d, J=6.58 Hz, 3H) 2.46-2.69 (m, 7H) 2.77 (s, 3H) 3.23 (t, J=4.24 Hz, 4H) 3.55 (q, J=6.77 Hz, 1H) 4.03 (s, 3H) 5.42 (s, 2H) 8.04 (d, J=2.19 Hz, 1H) 8.20-8.37 (m, 2H) 8.70 (d, J=1.90 Hz, 1H) 11.90 (s, 1H). m/z (ESI, +ve ion) 518.2 (M+H)+.

Workup

  1. temperatureThe mixture was cooled down to 20° C.
  2. stirringThe reaction mixture was stirred at room temperature for 5 h
  3. extractionextracted with CH2Cl2 (2×20 mL)
  4. washThe combined organic extracts were washed with saturated NaCl (5 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationThe solution was filtered
  7. concentrationconcentrated in vacuo
  8. customto give the crude material as a yellow solid
  9. customThe crude product was purified by silica gel chromatography
  10. washeluting with 5% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-d187e4b39abf47b595585a0f6535ff6c
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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