Water → HCID 68284359, compound

HRID 1527534Notes

Reaction equation

HRID 1527534 reaction equation
[NH2:1][CH2:2][C@@H:3]1[CH2:7][C@@H:6]([F:8])[CH2:5][N:4]1[C:9]([NH:11][C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[N:14]([C:21]([NH2:23])=[O:22])[CH:13]=1)=[O:10].Cl[C:25]([O:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:26].C(N(CC)CC)C.O>C(Cl)Cl>[C:28]1([O:27][C:25](=[O:26])[NH:1][CH2:2][C@@H:3]2[CH2:7][C@@H:6]([F:8])[CH2:5][N:4]2[C:9](=[O:10])[NH:11][C:12]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[N:14]([C:21](=[O:22])[NH2:23])[CH:13]=2)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 68283560HCID 68283560, compound

Product 1

HCID 68284359HCID 68284359, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 3-[((2S,4R)-2-aminomethyl-4-fluoro-pyrrolidine-1-carbonyl)-amino]-indole-1-carboxylic acid amide (50 mg, 0.157 mmol, prepared as described in Scheme B11) and phenyl chloroformate (22 μL, 0.17 mmol) in CH2Cl2 (0.5 mL), was added triethylamine (24 μL, 0.17 mmol) and the resulting suspension was stirred at RT under nitrogen overnight. The mixture was poured into water and extracted with CH2Cl2 (×2). The combined organic layers were dried (Na2SO4), filtered and concentrated. The crude residue was purified by preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 19×50 mm, eluent: 20% to 100% CH3CN in H2O in 15 min, CH3CN and H2O containing 0.1% HCOOH, flow: 20 mL/min) to give after lyophilization of the purified fractions the desired material. Rf, TLC (EtOAc)=0.45; MS (LC-MS): 440 [M+H]+, 901.3 [2M+Na]+; tR (HPLC conditions f): 1.77 min.

Workup

  1. extractionextracted with CH2Cl2 (×2)
  2. dry with materialThe combined organic layers were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude residue was purified by preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 19×50 mm, eluent: 20% to 100% CH3CN in H2O in 15 min, CH3CN and H2O containing 0.1% HCOOH, flow: 20 mL/min)
  6. customto give after lyophilization of the
  7. custompurified fractions the desired material
  8. custom1.77 min.

Sources & evidence

ORD record
ord-91e73a1edca74f55a3867867c7c70a0b
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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