Ethylenediamine → HCID 44224224, compound

HRID 1615849Notes

Reaction equation

HRID 1615849 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@@:9]2([CH3:56])[N:18]([CH2:19]/[CH:20]=[CH:21]/[C:22]3[CH:23]=[C:24]4[C:45](=[CH:46][CH:47]=3)[CH2:44][C:26]3([C:34]5[C:29](=[N:30][CH:31]=[CH:32][CH:33]=5)[N:28](COCC[Si](C)(C)C)[C:27]3=[O:43])[CH2:25]4)[C:17](=[O:48])[C:12]3([CH2:16][CH2:15][CH2:14][CH2:13]3)[N:11](C(OC(C)(C)C)=O)[CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1.C(O)(C(F)(F)F)=O.[OH-].[Na+].C(N)CN>C(Cl)Cl>[F:8][C:6]1[CH:5]=[C:4]([C@@:9]2([CH3:56])[N:18]([CH2:19]/[CH:20]=[CH:21]/[C:22]3[CH:23]=[C:24]4[C:45](=[CH:46][CH:47]=3)[CH2:44][C:26]3([C:34]5[C:29](=[N:30][CH:31]=[CH:32][CH:33]=5)[NH:28][C:27]3=[O:43])[CH2:25]4)[C:17](=[O:48])[C:12]3([CH2:13][CH2:14][CH2:15][CH2:16]3)[NH:11][CH2:10]2)[CH:3]=[C:2]([F:1])[CH:7]=1

Participants

6

Reactant 4

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 86650288HCID 86650288, compound

Product 1

HCID 44224224HCID 44224224, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl (8R)-8-(3,5-difluorophenyl)-8-methyl-10-oxo-9-[(2E)-3-(2′-oxo-1′-{[2-(trimethylsilyl)ethoxy]methyl}-1,1′,2′,3-tetrahydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-5-yl)prop-2-en-1-yl]-6,9-diazaspiro[4.5]decane-6-carboxylate from Step A above (0.2276 g, 0.290 mmol) was dissolved in DCM (5 mL). To this solution was added 1 mL of TFA. The reaction was stirred for 24 hours, then concentrated in vacuo. The residue was dissolved in MeOH (5 mL) and to this solution was added 1N NaOH (2.90 ml, 2.90 mmol), and ethylenediamine (0.078 ml, 1.160 mmol). The reaction was stirred for ½ hour at RT, then concentrated in vacuo. The residue was partitioned between ethyl acetate and water. The layers were separated, then the aqueous layer was washed 3×20 mL with ethyl acetate. The combined organic layers were washed with brine. Dried over Magnesium sulfate, filtered and concentrated in vacuo to yield the title compound. Diastereomer separation was accomplished using a Chiralcel OJ column, eluting with CO2:MeOH—70:30. Two peaks were isolated. Peak 1 MS: m/z=555 (M+1) HRMS: m/z=555.2569 (M+1); calculated m/z=555.2566 (M+1) for C33H32F2N4O2, and Peak 2 MS: m/z=555 (M+1)HRMS: m/z=555.2569 (M+1); calculated m/z=555.2566 (M+1) for C33H33F2N4O2.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in MeOH (5 mL) and to this solution
  3. stirringThe reaction was stirred for ½ hour at RT
  4. concentrationconcentrated in vacuo
  5. customThe residue was partitioned between ethyl acetate and water
  6. customThe layers were separated
  7. washthe aqueous layer was washed 3×20 mL with ethyl acetate
  8. washThe combined organic layers were washed with brine
  9. dry with materialDried over Magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-41275f09ae774169af104206f2843fae
Source dataset
uspto-grants-2014_07
Patent number
US08765759B2

Reaction notes

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