Hydrochloric Acid → HCID 59593036, compound

HRID 2098785Notes

Reaction equation

HRID 2098785 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[C:5]2[S:10][C:9]([CH2:11][NH2:12])=[CH:8][C:6]=2[N:7]=1.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)O.C(N(CC)C(C)C)(C)C.C([NH:50][CH2:51][C:52]([OH:54])=O)(OC(C)(C)C)=O.Cl.NO.Cl.CC1(C)C(C)(C)OB([C:67]2[CH:75]=[CH:74][CH:73]=[C:72]3[C:68]=2[CH:69]=[N:70][NH:71]3)O1>CN(C=O)C.C(Cl)Cl.O1CCOCC1.CCOCC.CO>[NH:71]1[C:72]2[C:68](=[C:67]([C:2]3[N:3]=[C:4]([N:13]4[CH2:18][CH2:17][O:16][CH2:15][CH2:14]4)[C:5]4[S:10][C:9]([CH2:11][NH:12][C:52](=[O:54])[CH2:51][NH2:50])=[CH:8][C:6]=4[N:7]=3)[CH:75]=[CH:74][CH:73]=2)[CH:69]=[N:70]1

Participants

13

Reactant 7

HCID 313Hydrochloric AcidHCID 78288N-(tert-butoxycarbonyl)glycineHCID 81531DiisopropylethylamineHCID 443297Hydroxyamine hydrochlorideHCID 21864398Tetramethyluronium hexafluorophosphateHCID 454801864-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazoleHCID 46180727(2-Chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methanamine

Product 1

HCID 59593036HCID 59593036, compound

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of (2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methanamine 27 from Example 11 (150 mg, 0.5 mmol) in DMF (4.5 mL) was added O-(7-azabenzotriazol-1-yl)-(N,N,N′,N′-tetramethyluronium hexafluorophosphate (400 mg, 1 mmol), N,N-diisopropylethylamine (550 μL, 3.2 mmol), then N-Boc glycine (270 mg, 1.5 mmol). The resulting solution stirred 30 min at room temperature. Excess hydroxylamine hydrochloride was added then the reaction was quenched with saturated aqueous NaHCO3. The aqueous layer was extracted with EtOAc. The combined organics were dried over Na2SO4, filtered, and concentrated in vacuo. A portion of the crude product (0.5 mmol) was dissolved in CH2Cl2 (15 mL), MeOH (15 mL), Et2O (6 mL), and 4 M HCl in dioxane (6 mL) was added. The resulting mixture stirred at room temperature overnight. The reaction mixture was concentrated in vacuo. A portion of the crude material (0.2 mmol) was utilized in a Suzuki coupling according to General Procedure A using 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole 7 to provide 331 after reverse phase HPLC purification (2 mg). MS (Q1) 424 (M)+

Workup

  1. customthe reaction was quenched with saturated aqueous NaHCO3
  2. extractionThe aqueous layer was extracted with EtOAc
  3. dry with materialThe combined organics were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. stirringThe resulting mixture stirred at room temperature overnight
  7. concentrationThe reaction mixture was concentrated in vacuo

Sources & evidence

ORD record
ord-507d82d69bca46d69dd06448baf35d92
Source dataset
uspto-grants-2013_05
Patent number
US08450315B2

Reaction notes

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