Diisopropylethylamine → Tert-butyl 4-(2-chloro-4-(5-(2-cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-6-methylphenoxy)butanoate

HRID 2278798Notes

Reaction equation

HRID 2278798 reaction equation
[CH:1]1([C:6]2[CH:7]=[C:8]([CH:12]=[C:13]([O:15][CH3:16])[N:14]=2)[C:9]([OH:11])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C.[Cl:48][C:49]1[CH:65]=[C:64]([C:66](=[NH:69])[NH:67]O)[CH:63]=[C:62]([CH3:70])[C:50]=1[O:51][CH2:52][CH2:53][CH2:54][C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56]>CN(C=O)C>[Cl:48][C:49]1[CH:65]=[C:64]([C:66]2[N:67]=[C:9]([C:8]3[CH:12]=[C:13]([O:15][CH3:16])[N:14]=[C:6]([CH:1]4[CH2:2][CH2:3][CH2:4][CH2:5]4)[CH:7]=3)[O:11][N:69]=2)[CH:63]=[C:62]([CH3:70])[C:50]=1[O:51][CH2:52][CH2:53][CH2:54][C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate2×HCID 584180372-Cyclopentyl-6-methoxyisonicotinic acidHCID 178426666HCID 178426666, compound

Product 1

HCID 70559037Tert-butyl 4-(2-chloro-4-(5-(2-cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-6-methylphenoxy)butanoateYield 41.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 2-cyclopentyl-6-methoxy-isonicotinic acid (33 mg, 0.149 mmol), TBTU (50 mg, 0.156 mmol) and DIPEA (62 mg, 0.479 mmol) in DMF (2 mL) is stirred at rt for 15 min before tert-butyl 4-(2-chloro-4-(N-hydroxycarbamimidoyl)-6-methylphenoxy)butanoate (51 mg, 0.149 mmol) is added. The mixture is stirred at rt for 1 h before another portion of TBTU (50 mg, 0.156 mmol) is added. Stirring is continued at rt for 2 h. The mixture is heated to 110° C. and stirring is continued for another hour. The mixture is concentrated and the crude product is purified by prep. HPLC to give tert-butyl 4-(2-chloro-4-(5-(2-cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-6-methylphenoxy)butanoate (33 mg) as a colourless glass; LC-MS: tR=1.28 min, [M+H]+=528.37.

Workup

  1. additionis added
  2. additionis added
  3. stirringstirring
  4. waitis continued for another hour
  5. concentrationThe mixture is concentrated
  6. customthe crude product is purified by prep

Sources & evidence

ORD record
ord-9efe0e15bb0f4b819e0b2e7ed804e9a9
Source dataset
uspto-grants-2015_09
Patent number
US09133179B2

Reaction notes

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