Tert-butyl 3-aminoazetidine-1-carboxylate → HCID 58204134, compound

HRID 1190634Notes

Reaction equation

HRID 1190634 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[O:14][CH2:13][CH2:12][C:11]3[CH:10]=[C:9]([C:15]4[N:16]([C:20]5[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=5[F:27])[N:17]=[CH:18][N:19]=4)[S:8][C:7]=3[C:6]=2[N:28]=1.[NH2:29][CH:30]1[CH2:33][N:32]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:31]1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C(O[Na])(C)(C)C>CC([O-])=O.CC([O-])=O.[Pd+2].O1CCOCC1>[C:37]([O:36][C:34]([N:32]1[CH2:33][CH:30]([NH:29][C:2]2[CH:3]=[CH:4][C:5]3[O:14][CH2:13][CH2:12][C:11]4[CH:10]=[C:9]([C:15]5[N:16]([C:20]6[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=6[F:27])[N:17]=[CH:18][N:19]=5)[S:8][C:7]=4[C:6]=3[N:28]=2)[CH2:31]1)=[O:35])([CH3:40])([CH3:38])[CH3:39]

Participants

7

Reactant 4

HCID 1516507Tert-butyl 3-aminoazetidine-1-carboxylateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 579003099-Chloro-2-[2-(2,4-difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azuleneHCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 58204134HCID 58204134, compoundYield 64%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
112 °C

Procedure

9-Chloro-2-[2-(2,4-difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulene (812 mg, 2.0 mmol), tert-butyl 3-aminoazetidine-1-carboxylate (412 mg, 2.4 mmol), Pd(OAc)2 (45 mg, 0.20 mmol), Xphos (95 mg, 2.0 mmol), t-BuONa (460 mg, 4.0 mmol) and dioxane (4.0 mL) were added into a 10 mL of sealed tube, and the mixture was heated by microwave at 112° C. for 7 min under N2. The reaction mixture was filtered to gather the solution and water was added. The mixture was extracted by DCM (20 mL×3). The combined organic layers were dried over Na2SO4, concentrated in vacuo, and purified by column (DCM/EtOAc=10:1) to give 3-{2-[2-(2,4-Difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulen-9-ylamino}-azetidine-1-carboxylic acid tert-butyl ester (703 mg, yield: 64%). 1HNMR (Acetone-d6, 400 MHz): δ7.99 (s, 1H), 7.76-7.73 (m, 1H), 7.38-7.27 (m, 2H), 7.14 (s, 1H), 7.00 (d, J=8.8 Hz, 1H), 6.37 (d, J=8.8 Hz, 1H), 6.27 (d, J=5.2 Hz, 1H), 4.29-4.09 (m, 6H), 3.57 (s, 1H), 3.02 (t, J=4.8 Hz, 2H), 1.34 (s, 9H). ESI-MS: m/z=553 [M+H+]

Workup

  1. filtrationThe reaction mixture was filtered
  2. additionwas added
  3. extractionThe mixture was extracted by DCM (20 mL×3)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. custompurified by column (DCM/EtOAc=10:1)

Sources & evidence

ORD record
ord-535b9153e9f1415ba318036fba615074
Source dataset
uspto-grants-2014_03
Patent number
US08673952B2

Reaction notes

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