Triethylamine → HCID 68313780, compound

HRID 2069138Notes

Reaction equation

HRID 2069138 reaction equation
[N+:1]([C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]([O:14][C:15]2[CH:20]=[CH:19][N:18]=[C:17]([NH2:21])[CH:16]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2].CCN(CC)CC.[C:29](Cl)(=O)[O:30]C1C=CC=CC=1.[CH3:39][N:40]([CH3:46])[C@@H:41]1[CH2:45][CH2:44][NH:43][CH2:42]1>C1COCC1>[CH3:39][N:40]([CH3:46])[C@@H:41]1[CH2:45][CH2:44][N:43]([C:29]([NH:21][C:17]2[CH:16]=[C:15]([O:14][C:7]3[C:8]4[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=4)[C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=3)[CH:20]=[CH:19][N:18]=2)=[O:30])[CH2:42]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 2758521(3R)-(+)-3-(Dimethylamino)pyrrolidine2×HCID 585325624-(4-Nitronaphthalen-1-yloxy)pyridin-2-amine

Product 1

HCID 68313780HCID 68313780, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-(4-nitronaphthalen-1-yloxy)pyridin-2-amine (200 mg, 0.71 mmol) and Et3N (0.20 mL, 1.42 mmol) in dry THF was added phenyl carbonochloridate (98 μL, 0.78 mmol) and the reaction mixture maintained at RT for 1 hr. An aliquot of (R)—N,N-dimethylpyrrolidin-3-amine (270 μL, 2.13 mmol) was added to this mixture and after 15 hr at RT a second aliquot of (R)—N,N-dimethylpyrrolidin-3-amine (100 μL, 0.79 mmol) was added and the mixture was maintained at RT for a further 1 hr. The resulting mixture was partitioned between aq. NH4Cl (10 mL) and DCM (10 mL) and the aqueous layer was separated and extracted with DCM (3×10 mL) The combined organic extracts were dried (MgSO4) and evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 40 g, [5% MeOH in DCM] in DCM, 0-100%, gradient elution and then, 10% [2% NH3 (7M in MeOH) in MeOH] in DCM, isocratic elution and finally, 30% MeOH in DCM, isocratic elution) to afford (R)-3-(dimethylamino)-N-(4-(4-nitronaphthalen-1-yloxy)pyridin-2-yl)pyrrolidine-1-carboxamide, Intermediate K1, as a yellow/brown solid (250 mg, 81%); Rt 1.54 min (Method 2); m/z 422 (M+H)+ (ES+).

Workup

  1. additionwas added
  2. temperaturethe mixture was maintained at RT for a further 1 hr
  3. customThe resulting mixture was partitioned between aq. NH4Cl (10 mL) and DCM (10 mL)
  4. customthe aqueous layer was separated
  5. extractionextracted with DCM (3×10 mL) The combined organic extracts
  6. dry with materialwere dried (MgSO4)
  7. customevaporated in vacuo
  8. customThe residue was purified by flash column chromatography (SiO2, 40 g, [5% MeOH in DCM] in DCM
  9. wash0-100%, gradient elution
  10. wash10% [2% NH3 (7M in MeOH) in MeOH] in DCM, isocratic elution
  11. washfinally, 30% MeOH in DCM, isocratic elution)

Sources & evidence

ORD record
ord-51e38a84bd4f4d61bcc8115fe0e14c52
Source dataset
uspto-grants-2012_10
Patent number
US08299074B2

Reaction notes

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