Ammonia → HCID 59548416, compound

HRID 1621835Notes

Reaction equation

HRID 1621835 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:35][CH3:36])=[CH:33][CH:34]=2)[CH:13]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].N>O1CCCC1.C(O[Ti](OC(C)C)(OC(C)C)OC(C)C)(C)C.C(Cl)Cl>[CH3:36][O:35][C:32]1[N:31]=[CH:30][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:34][CH:33]=1

Participants

8

Reactant 4

HCID 222AmmoniaHCID 7091611-(Methylsulfonyl)piperazineHCID 5049666Sodium triacetoxyborohydrideHCID 59548354HCID 59548354, compound

Product 1

HCID 59548416HCID 59548416, compoundYield 61.2%

Reagents, catalysts & solvents 3

HCID 178460666HCID 178460666, compoundCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of 1-(methylsulfonyl)piperazine (5.61 mg, 0.034 mmol, Apollo), 1-(6-(6-amino-2-methylpyrimidin-4-yl)-5-(6-methoxypyridin-3-ylamino)pyrazin-2-yl)ethanone (6 mg, 0.017 mmol) and tetraisopropoxytitanium (19.41 mg, 0.068 mmol, Aldrich) in tetrahydrofuran (0.5 mL) was stirred at 75° C. for 48 h. The mixture was cooled down to 20° C. and CH2Cl2 (1 mL) was added followed by sodium triacetoxyborohydride (14.48 mg, 0.068 mmol). The reaction mixture was stirred at room temperature for 5 h. Ammonia (1 mL, 30% in water) was added and the mixture was extracted with CH2Cl2 (2×10 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-(6-methoxypyridin-3-ylamino)-6-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyrazin-2-yl)-2-methylpyrimidin-4-amine (5.2 mg, 10.41 μmol, 61.0% yield). 1H NMR (300 MHz, CDCl3) δ 1.48 (d, J=6.87 Hz, 3H) 2.64 (s, 3H) 2.78 (s, 4H) 3.14-3.40 (m, 4H) 3.81 (q, J=6.72 Hz, 1H) 5.10 (s, 2H) 6.78 (d, J=8.77 Hz, 1H) 7.46 (s, 1H) 8.08 (dd, J=8.84, 2.70 Hz, 1H) 8.20 (s, 1H) 8.43 (d, J=2.63 Hz, 1H). m/z (ESI, +ve ion) 500.1 (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. extractionthe mixture was extracted with CH2Cl2 (2×10 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-503ac3cb051c49b2865cf7fef425d124
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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