Sodium Bicarbonate → HCID 68284229, compound

HRID 1527537Notes

Reaction equation

HRID 1527537 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:24][C:25]1[C:26]([F:33])=[C:27]([CH:30]=[CH:31][CH:32]=1)[CH:28]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.C([O-])(O)=O.[Na+]>ClC(Cl)C>[Cl:24][C:25]1[C:26]([F:33])=[C:27]([CH:30]=[CH:31][CH:32]=1)[CH2:28][NH: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]

Participants

7

Reactant 5

HCID 516892Sodium BicarbonateHCID 7363353-Chloro-2-fluorobenzaldehyde2×HCID 2724942TriacetoxyborohydrideHCID 5049666Sodium triacetoxyborohydrideHCID 68283560HCID 68283560, compound

Product 1

HCID 68284229HCID 68284229, compound

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

3-[((2S,4R)-2-Aminomethyl-4-fluoro-pyrrolidine-1-carbonyl)-amino]-indole-1-carboxylic acid amide (50 mg, 0.157 mmol) and 3-chloro-2-fluorobenzaldehyde (25 mg, 0.157 mmol, prepared as described in Scheme B11) were mixed in dichloroethane (1 mL), sodium triacetoxyborohydride (46.5 mg, 0.22 mmol) was added and the mixture was stirred at RT under nitrogen for 2 days. 3-Chloro-2-fluorobenzaldehyde (25 mg, 0.157 mmol) and triacetoxyborohydride (46.5 mg, 0.219 mmol) were added to complete the reaction. The reaction mixture was poured into a saturated aqueous solution of NaHCO3 and extracted with CH2Cl2. The combined organic extracts were dried (Na2SO4), filtered and concentrated. The crude residue diluted in MeOH was purified by SiliaPrep Tosic Acid-1 g (SPE-R60530B-06S from Silicycle), the column was washed with 10 mL of MeOH and the compound released with 10 mL of 2M ammonia in MeOH to give after concentration the desired material which was further 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 as a formic acid salt. MS (LC-MS): 462.1/464 [M+H]+, 460/462 [M−H]−; tR (HPLC, conditions f): 1.54 min.

Workup

  1. customthe reaction
  2. extractionextracted with CH2Cl2
  3. dry with materialThe combined organic extracts were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. additionThe crude residue diluted in MeOH
  7. customwas purified by SiliaPrep Tosic Acid-1 g (SPE-R60530B-06S from Silicycle)
  8. washthe column was washed with 10 mL of MeOH
  9. customto give
  10. concentrationafter concentration the desired material which
  11. customwas further 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)
  12. customto give after lyophilization of the
  13. custompurified fractions the desired material as a formic acid salt
  14. custom1.54 min.

Sources & evidence

ORD record
ord-d519753e285e489f9b9a36905fdeef43
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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