Morpholine → Tert-butyl 4-(4-(morpholine-4-carbonyl)thiazol-2-yl)-3-((pyridin-3-yloxy)methyl)piperazine-1-carboxylate

HRID 549756Notes

Reaction equation

HRID 549756 reaction equation
C(N=C=NC(C)C)(C)C.[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][N:20]([C:23]2[S:24][CH:25]=[C:26]([C:28]([OH:30])=O)[N:27]=2)[CH:19]([CH2:31][O:32][C:33]2[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=2)[CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11].[NH:39]1[CH2:44][CH2:43][O:42][CH2:41][CH2:40]1.C(N(C(C)C)CC)(C)C.ON1C2C=CC=CC=2N=N1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>C(Cl)Cl>[N:39]1([C:28]([C:26]2[N:27]=[C:23]([N:20]3[CH2:21][CH2:22][N:17]([C:15]([O:14][C:10]([CH3:11])([CH3:12])[CH3:13])=[O:16])[CH2:18][CH:19]3[CH2:31][O:32][C:33]3[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=3)[S:24][CH:25]=2)=[O:30])[CH2:44][CH2:43][O:42][CH2:41][CH2:40]1

Participants

8

Reactant 6

HCID 8083MorpholineHCID 12734DiisopropylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 596714672-(4-(Tert-butoxycarbonyl)-2-((pyridin-3-yloxy)methyl)piperazin-1-yl)thiazole-4-carboxylic acid

Product 1

HCID 66797341Tert-butyl 4-(4-(morpholine-4-carbonyl)thiazol-2-yl)-3-((pyridin-3-yloxy)methyl)piperazine-1-carboxylateYield 45%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Diisoproylcarbodiimide (0.028 mL, 0.178 mmol) was added to a solution of 2-(4-(tert-butoxycarbonyl)-2-((pyridin-3-yloxy)methyl)piperazin-1-yl)thiazole-4-carboxylic acid (68 mg, 0.162 mmol), morpholine (16 mg, 0.178 mmol), diisopropylethylamine (0.031 mL, 0.178 mmol), and N-hydroxybenzotriazole (24 mg, 0.178 mmol) in CH2Cl2 (2 mL). After stirring overnight, little reaction had taken place. TBTU (0.162 mmol) was added, and stirring was continued at rt for 4 h. The reaction mixture was quenched with 1 N NaOH (2 mL) and stirred for 1 h. The reaction mixture was diluted with EtOAc (20 mL) and was washed with 1 N NaOH (2×10 mL) and brine (10 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The material was purified by column chromatography (50 to 100% EtOAc in hexanes gradient), yielding 35.4 mg (45%) of the title compound. LC-MS: RT=6.77 min, [M+H]+=490.9. Rf=0.07 in 100% EtOAc.

Workup

  1. customlittle reaction
  2. stirringstirring
  3. waitwas continued at rt for 4 h
  4. customThe reaction mixture was quenched with 1 N NaOH (2 mL)
  5. stirringstirred for 1 h
  6. additionThe reaction mixture was diluted with EtOAc (20 mL)
  7. washwas washed with 1 N NaOH (2×10 mL) and brine (10 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe material was purified by column chromatography (50 to 100% EtOAc in hexanes gradient)

Sources & evidence

ORD record
ord-495b55b9ae81429497197614da13a04d
Source dataset
uspto-grants-2011_05
Patent number
US07943622B2

Reaction notes

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