Water → HCID 71009607, compound

HRID 1527532Notes

Reaction equation

HRID 1527532 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].[F:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[S:31](Cl)(=[O:33])=[O:32].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][S:31]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[F:24])(=[O:33])=[O:32])[CH2:7]1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 1377612-Fluorobenzenesulphonyl chlorideHCID 68283560HCID 68283560, compound

Product 1

HCID 71009607HCID 71009607, 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 (52 mg, 0.163 mmol) (prepared as described Scheme B11) and 2-fluorobenzenesulfonyl chloride (24 μL, 0.179 mmol) in CH2Cl2 (0.5 mL), was added triethylamine (25 μL, 0.179 mmol) and the resulting suspension was stirred at RT under nitrogen overnight. The mixture was poured into water and extracted twice with CH2Cl2. The combined organic layers were dried over 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)=0.55; MS (LC-MS): 478.1 [M+H]+, 500 [M+Na]+, 516 [M+K]+, 977.2 [2M+Na]+, 476 [M−H]−; tR (HPLC conditions f): 1.73 min.

Workup

  1. extractionextracted twice with CH2Cl2
  2. dry with materialThe combined organic layers were dried over 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. custom1.73 min.

Sources & evidence

ORD record
ord-3f4a402e54ee4ee8882e2bfb9abf7933
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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