Sodium Carbonate → 4-(4-(6-amino-5-methoxypyridin-3-yl)-2-tert-butyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-N-(2-methoxypyridin-4-yl)pyrimidin-2-amine

HRID 1091616Notes

Reaction equation

HRID 1091616 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:10]2[N:11]=[C:12]([C:30]([CH3:33])([CH3:32])[CH3:31])[NH:13][C:14]=2[C:15]2[CH:20]=[CH:19][N:18]=[C:17]([NH:21][C:22]3[CH:27]=[CH:26][N:25]=[C:24]([O:28][CH3:29])[CH:23]=3)[N:16]=2)=N[C:7]=1[O:8][CH3:9].BrC1N=C(C(C)(C)C)N([CH2:55][O:56][CH2:57][CH2:58][Si:59]([CH3:62])([CH3:61])[CH3:60])C=1C1C=CN=C(NC2C=CN=C(OC)C=2)N=1.[CH3:67]OC1C(N)=NC=C(B2OC(C)(C)C(C)(C)O2)N=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.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>[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:10]2[N:11]=[C:12]([C:30]([CH3:32])([CH3:31])[CH3:33])[N:13]([CH2:55][O:56][CH2:57][CH2:58][Si:59]([CH3:62])([CH3:61])[CH3:60])[C:14]=2[C:15]2[CH:20]=[CH:19][N:18]=[C:17]([NH:21][C:22]3[CH:27]=[CH:26][N:25]=[C:24]([O:28][CH3:29])[CH:23]=3)[N:16]=2)=[CH:67][C:7]=1[O:8][CH3:9]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 442307974-(4-(5-amino-6-methoxypyrazin-2-yl)-2-tert-butyl-1H-imidazol-5-yl)-N-(2-methoxypyridin-4-yl)pyrimidin-2-amineHCID 533986313-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazin-2-amineHCID 665912424-(4-bromo-2-tert-butyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-N-(2-methoxypyridin-4-yl)pyrimidin-2-amine

Product 1

HCID 665913124-(4-(6-amino-5-methoxypyridin-3-yl)-2-tert-butyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-N-(2-methoxypyridin-4-yl)pyrimidin-2-amineYield 69%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

Preparation of 4-(4-(5-amino-6-methoxypyrazin-2-yl)-2-tert-butyl-1H-imidazol-5-yl)-N-(2-methoxypyridin-4-yl)pyrimidin-2-amine: A mixture of 4-(4-bromo-2-tert-butyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-N-(2-methoxypyridin-4-yl)pyrimidin-2-amine (100 mg, 0.19 mmol), 3-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazin-2-amine (118 mg, 0.47 mmol, Example 18, Step 2), aqueous 2.0 M Na2CO3 solution (1 ml, 2.0 mmol), and Pd(PPh3)4 (22 mg, 0.019 mmol) in DME (2 mL) was sparged with N2 for 5 min. The reaction was sealed and heated to 100° C. for 2 h. The reaction was allowed to cool to rt, poured into EtOAc and partitioned with water. The layers were separated and the organic portion was washed with water, dried (MgSO4), and concentrated. The resulting residue was purified by flash chromatography (SiO2, 100:0-0:100, hexanes-25% MeOH in EtOAc) to afford 102 mg (69% purity) of 4-(4-(6-amino-5-methoxypyridin-3-yl)-2-tert-butyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-N-(2-methoxypyridin-4-yl)pyrimidin-2-amine: LCMS (m/z): 578.5 (MH+), tR=0.74 min.

Workup

  1. customwas sparged with N2 for 5 min
  2. customThe reaction was sealed
  3. temperatureto cool to rt
  4. additionpoured into EtOAc
  5. custompartitioned with water
  6. customThe layers were separated
  7. washthe organic portion was washed with water
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. customThe resulting residue was purified by flash chromatography (SiO2, 100:0-0:100, hexanes-25% MeOH in EtOAc)

Sources & evidence

ORD record
ord-db27fdd9b7d64e5da60607fa46f191df
Source dataset
uspto-grants-2012_03
Patent number
US08129394B2

Reaction notes

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