Hydrochloric Acid → HCID 178432266, compound

HRID 2273000Notes

Reaction equation

HRID 2273000 reaction equation
NC1N=C2C(C3C=CC(C(N4CCOCC4)=O)=CC=3)=NC=CN2N=1.CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C.[CH3:63][C:64]1[N:68](COCC[Si](C)(C)C)[C:67]2[CH:77]=[CH:78][C:79]([NH:81][C:82]3[N:104]=[C:85]4[C:86]([C:90]5[CH:95]=[CH:94][C:93]([C:96]([N:98]6[CH2:103][CH2:102][O:101][CH2:100][CH2:99]6)=[O:97])=[CH:92][CH:91]=5)=[N:87][CH:88]=[CH:89][N:84]4[N:83]=3)=[CH:80][C:66]=2[N:65]=1.Cl.C([O-])(O)=O.[Na+]>C(O)(C)(C)C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1COCC1.C(C1C=CC=CC=1)C.C(O)C>[CH3:63][C:64]1[NH:68][C:67]2[CH:77]=[CH:78][C:79]([NH:81][C:82]3[N:104]=[C:85]4[C:86]([C:90]5[CH:91]=[CH:92][C:93]([C:96]([N:98]6[CH2:99][CH2:100][O:101][CH2:102][CH2:103]6)=[O:97])=[CH:94][CH:95]=5)=[N:87][CH:88]=[CH:89][N:84]4[N:83]=3)=[CH:80][C:66]=2[N:65]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 25112535BrettphosHCID 89767234HCID 89767234, compoundHCID 89767315HCID 89767315, compound

Product 1

HCID 178432266HCID 178432266, compound

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 6386tert-ButanolSolventHCID 2733832Lithium HexamethyldisilazideSolventHCID 68569164HCID 68569164, compoundSolvent

Conditions

Temperature
110 °C

Procedure

[4-(2-Amino-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-phenyl]-morpholin-4-yl-methanone (see “C41”, 5-bromo-2-methyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazole (1.1 eq.), chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2′-4′-6′-tri-i-propyl-1,1′-biphenyl]2-(2-aminoethyl)phenyl)Pd(II) (0.03 eq), 2-(dicyclohexylphosphino)-3,6-dimethoxy-2′-4′-6′-tri-i-propyl-1,1′-biphenyl (0.03 eq) are dissolved in dry t-butanol under nitrogene, before lithium bis(trimethylsilyl)amide, (3 eq., 20% (ca 1.06M) solution in THF/ethylbenzene) is added. The resulting mixture is heated to 110° C. for 1 h. Work-up as described in general procedure 3 gives the SEM-protected intermediate. (4-{2-[2-Methyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-5-ylamino]-[1,2,4]triazolo[1,5-a]pyrazin-8-yl}-phenyl)-morpholin-4-yl-methanone is dissolved in ethanol. Concentrated HCl is added and the reaction mixture is heated to 65° C. for 4 h and monitored by LCMS. Upon completion, the mixture is neutralized with saturated NaHCO3-solution and the layers are separated, the aqueous phase is 3 times extracted with DCM. The combined organic phases are dried with Na2SO4 and concentrated. Purification gives the title compound as a solid.

Workup

  1. additionis added
  2. customgives the SEM-protected intermediate
  3. temperaturethe reaction mixture is heated to 65° C. for 4 h
  4. customthe layers are separated
  5. extractionextracted with DCM
  6. dry with materialThe combined organic phases are dried with Na2SO4
  7. concentrationconcentrated
  8. customPurification

Sources & evidence

ORD record
ord-186a67d1b9d04aadaaf902d6b45042d0
Source dataset
uspto-grants-2015_09
Patent number
US09120804B2

Reaction notes

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