Diisopropylcarbodiimide → HCID 59671565, compound

HRID 549754Notes

Reaction equation

HRID 549754 reaction equation
[CH:1]([N:4]=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](O)=[O:29])[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].Cl.CN.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>[CH3:1][NH:4][C:28]([C:26]1[N:27]=[C:23]([N:20]2[CH2:21][CH2:22][N:17]([C:15]([O:14][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:16])[CH2:18][CH:19]2[CH2:31][O:32][C:33]2[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=2)[S:24][CH:25]=1)=[O:29]

Participants

8

Reactant 6

HCID 12734DiisopropylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 6364545Methylamine hydrochloride2×HCID 596714672-(4-(Tert-butoxycarbonyl)-2-((pyridin-3-yloxy)methyl)piperazin-1-yl)thiazole-4-carboxylic acid

Product 1

HCID 59671565HCID 59671565, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

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), methylamine hydrochloride (12 mg, 0.178 mmol), diisopropylethylamine (0.062 mL, 0.357 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. After 4 h, additional methylamine hydrochloride (20 mg, 0.296 mmol) was added, and the reaction was heated to 50° C. in a sealed vial overnight. Upon cooling to rt, the reaction mixture was quenched with 1 N NaOH (4 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 (40 to 90% EtOAc in hexanes gradient), yielding 35 mg (50%) of the title compound. LC-MS: RT=6.77 min, [M+H]+=434.7. Rf=0.10 in 100% EtOAc.

Workup

  1. customlittle reaction
  2. stirringstirring
  3. customwas continued at rt
  4. waitAfter 4 h
  5. temperatureUpon cooling to rt
  6. customthe reaction mixture was quenched with 1 N NaOH (4 mL)
  7. stirringstirred for 1 h
  8. additionThe reaction mixture was diluted with EtOAc (20 mL)
  9. washwas washed with 1 N NaOH (2×10 mL) and brine (10 mL)
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customThe material was purified by column chromatography (40 to 90% EtOAc in hexanes gradient)

Sources & evidence

ORD record
ord-c6a88609e2134305803b0d4efe357eca
Source dataset
uspto-grants-2011_05
Patent number
US07943622B2

Reaction notes

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