Hydrazine → Tert-butyl[(1r)-1-(2,5-difluorobenzyl)-3-hydrazino-3-oxopropyl]carbamate

HRID 1863917Notes

Reaction equation

HRID 1863917 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:14][C:15]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=1[F:22])[CH2:10][C:11](O)=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].NN.O.O[N:27]1C2C=CC=CC=2N=[N:28]1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C>ClCCl>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]([CH2:14][C:15]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=1[F:22])[CH2:10][C:11]([NH:27][NH2:28])=[O:12])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 5

HCID 9321HydrazineHCID 81531Diisopropylethylamine2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 11347588(R)-b-(Boc-amino)-2,5-difluorobenzenebutanoic acid2×

Product 1

HCID 57973777Tert-butyl[(1r)-1-(2,5-difluorobenzyl)-3-hydrazino-3-oxopropyl]carbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 94.6 mg (0.3 mmol) of (3R)-3-[(tert-butoxycarbonyl)amino]-4-(2,5-difluorophenyl)butanoic acid (Intermediate 1) in 1.5 mL of anhydrous dichloromethane, stirred in an ice bath under protection from moisture, was added 0.0106 mL (10.8 mmol) of anhydrous 98% hydrazine. Then 91.8 mg of 1-hydroxybenzotriazole hydrate was added, followed by 63.4 mg (0.33 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and finally 0.0574 mL (42.6 mg, 0.33 mmol) of N,N-diisopropylethylamine. After 15 minutes, an additional 0.0574 mL (42.6 mg, 0.33 mmol) of N,N-diisopropylethylamine was added. After 2 h, the mixture was removed from the ice bath and allowed to warm to room temperature, and precipitation gradually increased. After 22 h, the precipitated solid was collected on a filter, washed with small volumes of dichloromethane, and dried to give the title compound as a white solid, mp 168-169° C. LC-MS 230 (M+1-Boc).

Workup

  1. waitAfter 2 h
  2. customthe mixture was removed from the ice bath
  3. customprecipitation
  4. temperaturegradually increased
  5. waitAfter 22 h
  6. customthe precipitated solid was collected on a filter
  7. washwashed with small volumes of dichloromethane
  8. customdried

Sources & evidence

ORD record
ord-85ab867d9c0b463c9ce0b26068aa180f
Source dataset
uspto-grants-2009_12
Patent number
US07625888B2

Reaction notes

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