Diisopropylethylamine → Tert-butyl [4-(5-benzyl[1.3.4]thiadiazol-2-ylcarbamoyl)phenyl]carbamate

HRID 1035701Notes

Reaction equation

HRID 1035701 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:17]=[CH:16][C:12]([C:13]([OH:15])=O)=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:18]([C:25]1[S:29][C:28]([NH2:30])=[N:27][N:26]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.Cl.C(N=C=NCCCN(C)C)C.OC1C2N=NNC=2C=CC=1.C(N(C(C)C)CC)(C)C>ClCCl.O.CN(C)C=O>[CH2:18]([C:25]1[S:29][C:28]([NH:30][C:13]([C:12]2[CH:11]=[CH:10][C:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[CH:17][CH:16]=2)=[O:15])=[N:27][N:26]=1)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 7548235-Benzyl-1,3,4-thiadiazol-2-amineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 27559314-{[(Tert-butoxy)carbonyl]amino}benzoic acidHCID 178418300HCID 178418300, compound2×

Product 1

HCID 86662112Tert-butyl [4-(5-benzyl[1.3.4]thiadiazol-2-ylcarbamoyl)phenyl]carbamateYield 11.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
60 °C

Procedure

1 g of 4-tert-butoxycarbonylaminobenzoic acid (4.21 mmol, 1 eq.) is placed in 12 mL of a 5/1 mixture of dichloromethane and dimethylformamide with stirring. 0.81 g of 5-benzyl-1,3,4-thiadiazol-2-amine (4.21 mmol, 1 eq.), 0.97 g of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (5.05 mmol, 1.2 eq.), 0.97 g of hydroxybenzotriazole (6.32 mmol, 1.5 eq.) and 1.74 mL of diisopropylethylamine (10.52 mmol, 2.5 eq.) are successively added. After 42 hours at room temperature, the medium is heated at 60° C. for 6 hours. 0.40 g of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.1 mmol, 0.5 eq.) and 0.322 g of hydroxybenzotriazole (3.16 mmol, 0.5 eq.) are added. After 18 hours, the medium is diluted with dichloromethane and water. The organic phase is separated out by settling, washed with water, dried over magnesium sulfate, filtered and evaporated. The residue is chromatographed on silica gel with a gradient of ethyl acetate in heptane ranging from 0% to 50%. The organic phase is evaporated to give 0.2 g of tert-butyl [4-(5-benzyl[1.3.4]thiadiazol-2-ylcarbamoyl)phenyl]carbamate.

Workup

  1. waitAfter 18 hours
  2. customThe organic phase is separated out
  3. washwashed with water
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue is chromatographed on silica gel with a gradient of ethyl acetate in heptane ranging from 0% to 50%
  8. customThe organic phase is evaporated

Sources & evidence

ORD record
ord-c8aeafb724114cfa973e7d5b6f26921d
Source dataset
uspto-grants-2013_10
Patent number
US08546391B2

Reaction notes

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