Water → (S)-6-(3-(4-chloro-5-fluoroindolin-1-yl)-2-oxopyrrolidin-1-yl)-N-(thiazol-2-yl)pyridine-3-sulfonamide

HRID 1670586Notes

Reaction equation

HRID 1670586 reaction equation
C(OC(N=NC(OC(C)(C)C)=O)=O)(C)(C)C.C(P(CCCC)CCCC)CCC.[Cl:30][C:31]1[C:39]([F:40])=[CH:38][CH:37]=[C:36]2[C:32]=1[CH2:33][CH2:34][N:35]2[C@@H:41]([CH2:60][CH2:61]O)[C:42]([NH:44][C:45]1[CH:50]=[CH:49][C:48]([S:51](=[O:59])(=[O:58])[NH:52][C:53]2[S:54][CH:55]=[CH:56][N:57]=2)=[CH:47][N:46]=1)=[O:43].O>C1COCC1>[Cl:30][C:31]1[C:39]([F:40])=[CH:38][CH:37]=[C:36]2[C:32]=1[CH2:33][CH2:34][N:35]2[C@H:41]1[CH2:60][CH2:61][N:44]([C:45]2[N:46]=[CH:47][C:48]([S:51]([NH:52][C:53]3[S:54][CH:55]=[CH:56][N:57]=3)(=[O:59])=[O:58])=[CH:49][CH:50]=2)[C:42]1=[O:43]

Participants

6

Reactant 4

HCID 962WaterHCID 13831TributylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 57665817(S)-2-(4-chloro-5-fluoroindolin-1-yl)-4-hydroxy-N-(5-(N-thiazol-2-ylsulfamoyl)pyridine-2-yl)butanamide

Product 1

HCID 25234773(S)-6-(3-(4-chloro-5-fluoroindolin-1-yl)-2-oxopyrrolidin-1-yl)-N-(thiazol-2-yl)pyridine-3-sulfonamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Prepared using General Procedure 3. To a stirring solution of di-tert-butyl-azodicarboxylate (44 mg, 0.05 mmol) and THF (0.5 mL), under N2, at 0° C., was added tributylphosphine (48 mg, 0.19 mmol), dropwise over 5 minutes. The colourless solution was stirred at 0° C. for 30 minutes. A solution of (S)-2-(4-chloro-5-fluoroindolin-1-yl)-4-hydroxy-N-(5-(N-thiazol-2-ylsulfamoyl)pyridine-2-yl)butanamide (24 mg, 0.05 mmol) in THF (0.5 mL) was added dropwise over 5 minutes. The solution was stirred at ambient temperature for 2 hours. To this solution was added H2O (40 uL) and the solution was evaporated to dryness. The residue was purified via reverse phase HPLC using 10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA) gave (S)-6-(3-(4-chloro-5-fluoroindolin-1-yl)-2-oxopyrrolidin-1-yl)-N-(thiazol-2-yl)pyridine-3-sulfonamide. LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=494.1; tR=1.69 min. 1H NMR (400 MHz, DMSO-d6) δ 8.78 (s, 1H), 8.43 (d, J=8.8 Hz, 1H), 8.20 (dd, J=8.9, 2.5 Hz, 1H), 7.30 (d, J=4.6 Hz, 1H), 7.01 (t, J=9.2 Hz, 1H), 6.87 (d, J=4.6 Hz, 1H), 6.48 (dd, J=8.7, 3.6 Hz, 1H), 4.89 (q, J=6.6 Hz, 1H), 4.18 (t, J=9.7 Hz, 1H), 3.84-3.77 (m, 1H), 3.65-3.59 (m, 1H), 3.39-3.37 (m, 1H), 3.05-2.98 (m, 2H), 2.38-2.31 (m, 1H), 2.21-2.10 (m, 1H).

Workup

  1. customPrepared
  2. stirringThe solution was stirred at ambient temperature for 2 hours
  3. customthe solution was evaporated to dryness
  4. customThe residue was purified via reverse phase

Sources & evidence

ORD record
ord-58ae09157da14b0ba3c9c163aa6b9e36
Source dataset
uspto-grants-2011_08
Patent number
US07994174B2

Reaction notes

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