Tetrahydrofuran → HCID 86726671, compound

HRID 1499419Notes

Reaction equation

HRID 1499419 reaction equation
C(OC([NH:8][C:9]1[S:13][C:12]([C:14]2[C:19]([F:20])=[CH:18][CH:17]=[CH:16][C:15]=2[F:21])=[N:11][C:10]=1[C:22]([NH:24][C:25]1[C:26]([N:43]2[CH2:48][CH2:47][CH2:46][C@H:45]([NH:49]C(=O)OC(C)(C)C)[CH2:44]2)=[C:27]2[CH:33]=[CH:32][N:31](S(C3C=CC=CC=3)(=O)=O)[C:28]2=[N:29][CH:30]=1)=[O:23])=O)(C)(C)C.C1COCC1>CO.[OH-].[Na+].CCOC(C)=O>[NH2:8][C:9]1[S:13][C:12]([C:14]2[C:15]([F:21])=[CH:16][CH:17]=[CH:18][C:19]=2[F:20])=[N:11][C:10]=1[C:22]([NH:24][C:25]1[C:26]([N:43]2[CH2:48][CH2:47][CH2:46][C@H:45]([NH2:49])[CH2:44]2)=[C:27]2[CH:33]=[CH:32][NH:31][C:28]2=[N:29][CH:30]=1)=[O:23]

Participants

6

Reactant 2

HCID 8028TetrahydrofuranHCID 86726670HCID 86726670, compound

Product 1

HCID 86726671HCID 86726671, compoundYield 41.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent

Procedure

To solution of tert-butyl {(3S)-1-[5-({[5-[(tert-butoxycarbonyl)amino]-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 (194.4 mg, 0.2400 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), then dried over Na2SO4 and concentrated under reduced pressure. The resulting 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 (46.6 mg, 41%). LCMS calc. for C22H22F2N7OS (M+H)+: m/z=470.1. found 470.2. 1H NMR (500 MHz, DMSO-d6) δ 11.49 (s, 1H), 9.49 (s, 1H), 9.04 (s, 1H), 7.64-7.47 (m, 3H), 7.35 (d, J=3.3 Hz, 1H), 7.27 (t, J=8.8 Hz, 2H), 6.57 (d, J=3.4 Hz, 1H), 3.29-3.23 (m, 1H), 3.10-3.03 (m, 1H), 3.00-2.86 (m, 2H), 2.85-2.77 (m, 1H), 1.87-1.79 (m, 1H), 1.79-1.65 (m, 2H), 1.24-1.10 (m, 1H) ppm.

Workup

  1. washwashed with brine (50 mL)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe resulting 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-7bf25523866d40fe88fc3afe82f86dc1
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

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