Ethyl Acetate → HCID 68283728, compound

HRID 1527604Notes

Reaction equation

HRID 1527604 reaction equation
[C:1]([C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]([CH2:13][C:14]([N:16]2[C@H:21]([C:22](=[O:36])[NH:23][C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([O:30][C:31]([F:34])([F:33])[F:32])[C:25]=3[F:35])[CH2:20][C@:19]3([CH2:37][O:38]C(=O)CN4C5C(=CC=CC=5)C(C(=O)N)=N4)[C@H:17]2[CH2:18]3)=[O:15])[N:5]=1)(=[O:3])[NH2:2].[OH-].[Na+].CCOC(C)=O>C1COCC1.O>[F:35][C:25]1[C:26]([O:30][C:31]([F:33])([F:34])[F:32])=[CH:27][CH:28]=[CH:29][C:24]=1[NH:23][C:22]([C@@H:21]1[CH2:20][C@:19]2([CH2:37][OH:38])[C@@H:17]([CH2:18]2)[N:16]1[C:14](=[O:15])[CH2:13][N:6]1[C:7]2[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:4]([C:1]([NH2:2])=[O:3])=[N:5]1)=[O:36]

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 86673885HCID 86673885, compound

Product 1

HCID 68283728HCID 68283728, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (3-carbamoyl-indazol-1-yl)-acetic acid (1R,3S,5S)-2-[2-(3-carbamoyl-indazol-1-yl)-acetyl]-3-(2-fluoro-3-trifluoromethoxy-phenylcarbamoyl)-2-aza-bicyclo[3.1.0]hex-5-ylmethyl ester (69.2 mg, 0.085 mmol) and NaOH (1N, 188 μL, 0.19 mmol) in THF (0.45 mL) and water (43 μL) was stirred at RT 1 h. Water and EtOAc were added, the layers were separated and the aqueous one extracted with EtOAc (×2). The combined organic extracts were dried (Na2SO4), filtered and concentrated. The crude residue was purified by preparative HPLC (Waters Sunfire C18-OBD, 5 μm, 30×100 mm, eluent: 20% to 100% CH3CN in H2O in 25 min, CH3CN and H2O containing 0.1% TFA, flow: 40 mL/min). Rf, TLC (CH2Cl2/MeOH 9:1)=0.45; MS (UPLC/MS): 536.4 [M+H]+, 553.3 [M+NH4]+, 558.2 [M+Na]+, 534.3 [M−H]−, 580.3 [M+HCOO]−; tR (HPLC conditions f): 1.82 min.

Workup

  1. customthe layers were separated
  2. extractionthe aqueous one extracted with EtOAc (×2)
  3. dry with materialThe combined organic extracts were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude residue was purified by preparative HPLC (Waters Sunfire C18-OBD, 5 μm, 30×100 mm, eluent: 20% to 100% CH3CN in H2O in 25 min, CH3CN and H2O containing 0.1% TFA, flow: 40 mL/min)
  7. custom1.82 min.

Sources & evidence

ORD record
ord-ae1671f511a44b0187c56b5dc926a0c5
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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