Tetrahydrofuran → HCID 86726673, compound

HRID 1499421Notes

Reaction equation

HRID 1499421 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[S:10][CH:11]=[C:12]([C:14]([NH:16][C:17]2[C:18]([N:35]3[CH2:40][CH2:39][CH2:38][C@H:37]([NH:41]C(=O)OC(C)(C)C)[CH2:36]3)=[C:19]3[CH:25]=[CH:24][N:23](S(C4C=CC=CC=4)(=O)=O)[C:20]3=[N:21][CH:22]=2)=[O:15])[N:13]=1.C1COCC1>CO.[OH-].[Na+].CCOC(C)=O>[NH2:41][C@H:37]1[CH2:38][CH2:39][CH2:40][N:35]([C:18]2[C:17]([NH:16][C:14]([C:12]3[N:13]=[C:9]([C:3]4[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=4[F:8])[S:10][CH:11]=3)=[O:15])=[CH:22][N:21]=[C:20]3[NH:23][CH:24]=[CH:25][C:19]=23)[CH2:36]1

Participants

6

Reactant 2

HCID 8028TetrahydrofuranHCID 86726672HCID 86726672, compound

Product 1

HCID 86726673HCID 86726673, compoundYield 52%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent

Procedure

To a solution of tert-butyl {(3S)-1-[5-({[2-(2,6-difluorophenyl)-1,3-thiazol-4-yl]carbonyl}amino)-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]piperidin-3-yl}carbamate (175.3 mg, 0.2523 mmol) in MeOH (2.0 mL), aq. NaOH (1.0 M, 2.0 mL) was added, followed by THF (2.0 mL). After stirring at room temperature for 5 h, the reaction mixture was diluted with EtOAc (50 mL), washed with brine (50 mL), dried over Na2SO4 and concentrated under reduced pressure. The residue was dissolved in DCM (2.0 mL), and TFA (2.0 mL) was added. The mixture was stirred at room temperature for 30 min., and then concentrated under reduced pressure. The resulting residue was purified using RP-HPLC (XBridge™ C18 column, eluting with a gradient of MeCN/water containing 0.15% NH4OH, at flow rate of 30 mL/min.) to afford the title compound as a white solid (59.1 mg, 52%). LCMS calc. for C22H22F2N6OS (M+H)+: m/z=455.1. found 455.1.

Workup

  1. washwashed with brine (50 mL)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue was dissolved in DCM (2.0 mL)
  5. additionTFA (2.0 mL) was added
  6. stirringThe mixture was stirred at room temperature for 30 min.
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue was purified
  9. washeluting with a gradient of MeCN/water containing 0.15% NH4OH, at flow rate of 30 mL/min.)

Sources & evidence

ORD record
ord-674e5955aee640b6b21a1887bf93363f
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

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