Hydrochloric Acid → HCID 59592945, compound

HRID 2262210Notes

Reaction equation

HRID 2262210 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+:27]([CH3:33])=C(N(C)C)O.C([N:37](CC)[CH:38]([CH3:40])[CH3:39])(C)C.C(NCC(O)=O)(O[C:46](C)([CH3:48])[CH3:47])=O.Cl.[NH2:56]O.Cl.[CH3:59][S:60](Cl)(=[O:62])=[O:61].[O:64]1[CH2:69][CH2:68]OCC1>CN(C=O)C.C(Cl)Cl.CCN(CC)CC.CCOCC.CO>[NH:37]1[C:38]2[C:39](=[C:47]([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:69](=[O:64])[CH2:68][NH:56][S:60]([CH3:59])(=[O:62])=[O:61])=[CH:8][C:6]=4[N:7]=3)[CH:46]=[CH:48][CH:40]=2)[CH:33]=[N:27]1

Participants

14

Reactant 8

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 31297Methanesulfonyl chlorideHCID 78288N-(tert-butoxycarbonyl)glycineHCID 81531DiisopropylethylamineHCID 443297Hydroxyamine hydrochlorideHCID 21864398Tetramethyluronium hexafluorophosphateHCID 46180727(2-Chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methanamine

Product 1

HCID 59592945HCID 59592945, compound

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

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 (0.3 mmol) was dissolved in CH2Cl2 (8 mL) and Et3N (4 mL) and methanesulfonyl chloride (450 μL, 6 mmol) was added. The reaction mixture stirred at room temperature overnight. The reaction was quenched by the addition of water then extracted with EtOAc. The combined organics were dried over Na2SO4, filtered, and concentrated in vacuo. The crude material 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 330 after reverse phase HPLC purification (36 mg). MS (Q1) 502 (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
  8. stirringThe reaction mixture stirred at room temperature overnight
  9. customThe reaction was quenched by the addition of water
  10. extractionthen extracted with EtOAc
  11. dry with materialThe combined organics were dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5f0c5a115f23420990403e2db3727c72
Source dataset
uspto-grants-2010_12
Patent number
US07846929B2

Reaction notes

Loading…