Diisopropylethylamine → {4-[5-(4-Benzyloxy-3-ethyl-5-methyl-phenyl)-[1,3,4]oxadiazol-2-yl]-6-methyl-pyrimidin-2-yl}-isopropyl-amine

HRID 2069424Notes

Reaction equation

HRID 2069424 reaction equation
[CH:1]([NH:4][C:5]1[N:10]=[C:9]([C:11]([OH:13])=O)[CH:8]=[C:7]([CH3:14])[N:6]=1)([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH2:46]([O:53][C:54]1[C:63]([CH3:64])=[CH:62][C:57]([C:58]([NH:60][NH2:61])=O)=[CH:56][C:55]=1[CH2:65][CH3:66])[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1.CC[N+](S(N=C(OC)[O-])(=O)=O)(CC)CC>CN(C=O)C.CCOC(C)=O.C1COCC1>[CH2:46]([O:53][C:54]1[C:63]([CH3:64])=[CH:62][C:57]([C:58]2[O:13][C:11]([C:9]3[CH:8]=[C:7]([CH3:14])[N:6]=[C:5]([NH:4][CH:1]([CH3:2])[CH3:3])[N:10]=3)=[N:61][N:60]=2)=[CH:56][C:55]=1[CH2:65][CH3:66])[C:47]1[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=1

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 2724994Methyl N-(triethylammoniosulfonyl)carbamateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 592020264-Benzyloxy-3-ethyl-5-methyl-benzoic acid hydrazideHCID 669337152-(Isopropylamino)-6-methylpyrimidine-4-carboxylic acid

Product 1

HCID 68506492{4-[5-(4-Benzyloxy-3-ethyl-5-methyl-phenyl)-[1,3,4]oxadiazol-2-yl]-6-methyl-pyrimidin-2-yl}-isopropyl-amineYield 56%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-isopropylamino-6-methyl-pyrimidine-4-carboxylic acid (200 mg, 1.02 mmol) and DIPEA (0.43 mL) in DMF (100 mL) is added TBTU (395 mg, 1.23 mmol). The reaction mixture is stirred at 0° C. for 15 min before adding 4-benzyloxy-3-ethyl-5-methyl-benzoic acid hydrazide. Stirring is continued for 1 h and the reaction mixture is then diluted with EtOAc and washed with sat. aq. NaHCO3. The aq. phase is extracted with EtOAc and the combined org. phases are dried over MgSO4, filtered and evaporated to give a brown oil. The oil is dissolved in THF (5.0 mL) and Burgess reagent (155 mg, 0.65 mmol) is added. The reaction mixture is heated to 110° C. for 15 min under microwave conditions. The reaction mixture is evaporated and purified by prep. TLC (eluting with Heptane/EA 9:1) to afford {4-[5-(4-benzyloxy-3-ethyl-5-methyl-phenyl)-[1,3,4]oxadiazol-2-yl]-6-methyl-pyrimidin-2-yl}-isopropyl-amine as a yellow oil (125 mg, 56%); LC-MS: tR=1.16; [M+H]+=444.08.

Workup

  1. stirringStirring
  2. waitis continued for 1 h
  3. washwashed with sat. aq. NaHCO3
  4. extractionThe aq. phase is extracted with EtOAc
  5. dry with materialphases are dried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customto give a brown oil
  9. temperatureThe reaction mixture is heated to 110° C. for 15 min under microwave conditions
  10. customThe reaction mixture is evaporated
  11. custompurified by prep
  12. washTLC (eluting with Heptane/EA 9:1)

Sources & evidence

ORD record
ord-b1368d7da6b9422ca9e9b120cfaa692b
Source dataset
uspto-grants-2012_10
Patent number
US08299086B2

Reaction notes

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