Triethylamine → {(S)-1-[2-(Tetrahydropyran-3-ylamino)phenylcarbamoyl]ethyl}carbamic acid tertbutyl ester

HRID 242831Notes

Reaction equation

HRID 242831 reaction equation
CCN(CC)CC.[O:8]1[CH2:13][CH2:12][CH2:11][CH:10]([NH:14][C:15]2[C:16]([NH2:21])=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:9]1.[C:22]([O:26][C:27]([NH:29][C@@H:30]([CH3:34])[C:31](O)=[O:32])=[O:28])([CH3:25])([CH3:24])[CH3:23].C1C=NC2N(O)N=NC=2C=1.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl>[C:22]([O:26][C:27](=[O:28])[NH:29][C@H:30]([C:31](=[O:32])[NH:21][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=1[NH:14][CH:10]1[CH2:11][CH2:12][CH2:13][O:8][CH2:9]1)[CH3:34])([CH3:23])([CH3:24])[CH3:25]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 85082Tert-butoxycarbonylalanineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 63360336N-(Tetrahydropyran-3-yl)benzene-1,2-diamine

Product 1

HCID 68158389{(S)-1-[2-(Tetrahydropyran-3-ylamino)phenylcarbamoyl]ethyl}carbamic acid tertbutyl esterYield 83.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Et3N (1.6 mL, 11.3 mmol) was added to a stirred mixture of N-(tetrahydropyran-3-yl)benzene-1,2-diamine (0.61 g, 3.17 mmol), (S)-2-tertbutoxycarbonylaminopropionic acid (0.78 g, 4.14 mmol), HOAt (0.56 g, 4.14 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.79 g, 4.14 mmol) in anhydrous DCM (20 mL) at 0° C. under a nitrogen atmosphere. Stirring was continued for 10 min at 0° C. then the mixture was slowly warmed to RT and stirred at RT for 3 h. The reaction mixture was partitioned between DCM and a saturated solution of NaHCO3. The aqueous phase was further extracted with DCM (×2) and the combined organic layers were washed with brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-4% 2M NH3/MeOH in DCM) affording {(S)-1-[2-(Tetrahydropyran-3-ylamino)phenylcarbamoyl]ethyl}carbamic acid tertbutyl ester as a white solid (0.96 g, 70%). LCMS: RT 3.00 min [M+H]+ 364.1.

Workup

  1. stirringstirred at RT for 3 h
  2. customThe reaction mixture was partitioned between DCM
  3. extractionThe aqueous phase was further extracted with DCM (×2)
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-4% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-13abb46976f14e2cb6dc8fddeb1da206
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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