Water → HCID 68283284, compound

HRID 1527533Notes

Reaction equation

HRID 1527533 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].[C:24]1([CH2:30][C:31](Cl)=[O:32])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(N(CC)CC)C.O>C(Cl)Cl>[F:8][C@H:6]1[CH2:5][N:4]([C:9]([NH:11][C:12]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[N:14]([C:21]([NH2:23])=[O:22])[CH:13]=2)=[O:10])[C@H:3]([CH2:2][NH:1][C:31](=[O:32])[CH2:30][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:7]1

Participants

6

Reactant 4

HCID 962WaterHCID 7679Phenylacetyl chlorideHCID 8471TriethylamineHCID 68283560HCID 68283560, compound

Product 1

HCID 68283284HCID 68283284, 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, 0.16 mmol, prepared as described in Scheme B11) and phenylacetyl chloride (23 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 N2 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)=0.1; MS (LC-MS): 438.1 [M+H]+, 897.2 [2M+Na]+, 393.1 [M−CONH2]−; tR (HPLC conditions f): 1.70 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. custom1.70 min.

Sources & evidence

ORD record
ord-a86d279549594513a2e11d10e7373c89
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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