Ethylamine → HCID 69675083, compound

HRID 575504Notes

Reaction equation

HRID 575504 reaction equation
[C:1]([CH2:3][CH:4]([N:23]1[CH:27]=[C:26]([C:28]2[C:29]3[CH:36]=[CH:35][N:34](COCC[Si](C)(C)C)[C:30]=3[N:31]=[CH:32][N:33]=2)[CH:25]=[N:24]1)[CH2:5][N:6]1[CH2:11][CH2:10][CH:9]([O:12][C:13]2[CH:14]=[C:15]([CH:19]=[C:20]([F:22])[CH:21]=2)[C:16](O)=[O:17])[CH2:8][CH2:7]1)#[N:2].[CH2:45]([NH2:47])[CH3:46].C1COCC1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>C(Cl)Cl.CN(C)C=O>[C:1]([CH2:3][CH:4]([N:23]1[CH:27]=[C:26]([C:28]2[C:29]3[CH:36]=[CH:35][NH:34][C:30]=3[N:31]=[CH:32][N:33]=2)[CH:25]=[N:24]1)[CH2:5][N:6]1[CH2:7][CH2:8][CH:9]([O:12][C:13]2[CH:14]=[C:15]([CH:19]=[C:20]([F:22])[CH:21]=2)[C:16]([NH:47][CH2:45][CH3:46])=[O:17])[CH2:10][CH2:11]1)#[N:2]

Participants

8

Reactant 5

HCID 6341EthylamineHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 69675261HCID 69675261, compound

Product 1

HCID 69675083HCID 69675083, compoundYield 18%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 3-[(1-{3-cyano-2-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propyl}piperidin-4-yl)oxy]-5-fluorobenzoic acid (18 mg, 0.029 mmol) and 2.0 M ethylamine in THF (21.8 μL, 0.0436 mmol) in methylene chloride (0.2 mL) and dimethylformamide (DMF) (50 μL) were added triethylamine (6.1 μL, 0.0436 mmol) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (19.3 mg, 0.0436 mmol). The resulting mixture was stirred overnight at room temperature and concentrated. To the residue was added saturated NaHCO3 solution then extracted with ethyl acetate (3×). The combined extracts were dried over MgSO4, filtered, and concentrated. The crude residue was dissolved in DCM (0.2 mL) and TFA (0.2 mL). The mixture was stirred for 2 hours then concentrated. To the reaction vial was added MeOH (0.5 mL) and ethylenediamine (EDA) (0.1 mL). After stirring for 1 hour, the mixture was diluted with acetonitrile and purified by preparative-LCMS (eluting with a gradient of ACN/H2O containing 0.15% NH4OH) to afford the desired product (2.7 mg, 18%). LCMS (M+H)+: 517.3.

Workup

  1. concentrationconcentrated
  2. additionTo the residue was added saturated NaHCO3 solution
  3. extractionthen extracted with ethyl acetate (3×)
  4. dry with materialThe combined extracts were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe crude residue was dissolved in DCM (0.2 mL)
  8. stirringThe mixture was stirred for 2 hours
  9. concentrationthen concentrated
  10. additionTo the reaction vial was added MeOH (0.5 mL) and ethylenediamine (EDA) (0.1 mL)
  11. stirringAfter stirring for 1 hour
  12. additionthe mixture was diluted with acetonitrile
  13. custompurified by preparative-LCMS (
  14. washeluting with a gradient of ACN/H2O containing 0.15% NH4OH)

Sources & evidence

ORD record
ord-644bb725a19c461b81418d63a47d13ea
Source dataset
uspto-grants-2015_05
Patent number
US09034884B2

Reaction notes

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