Tetrahydrofuran → 4-Chloro-n-[5-chloro-2-(7h-pyrrolo[2,3-d]pyrimidine-4-carbonyl)-phenyl]-3-trifluoromethyl-benzenesulfonamide

HRID 1363058Notes

Reaction equation

HRID 1363058 reaction equation
[CH:1]([Mg]Cl)([CH3:3])C.I[C:7]1[NH:8]C2C(N=CC=2)=C[N:12]=1.CC1C=CC=C(C)C=1[Mg]Br.[Na].[Cl:27][C:28]1[CH:39]=[CH:38][C:31](C(N(OC)C)=O)=[C:30]([NH:40][S:41]([C:44]2[CH:49]=[CH:48][C:47]([Cl:50])=[C:46]([C:51]([F:54])([F:53])[F:52])[CH:45]=2)(=[O:43])=[O:42])[CH:29]=1.[H-].[Na+].[NH4+:57].[Cl-].[CH2:59]1[CH2:63][O:62][CH2:61][CH2:60]1>>[Cl:50][C:47]1[CH:48]=[CH:49][C:44]([S:41]([NH:40][C:30]2[CH:29]=[C:28]([Cl:27])[CH:39]=[CH:38][C:31]=2[C:63]([C:59]2[C:60]3[CH:3]=[CH:1][NH:57][C:61]=3[N:8]=[CH:7][N:12]=2)=[O:62])(=[O:42])=[O:43])=[CH:45][C:46]=1[C:51]([F:52])([F:53])[F:54]

Participants

9

Reactant 8

HCID 8028Tetrahydrofuran2×HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 5360545SodiumHCID 578708014-Chloro-2-(4-chloro-3-trifluoromethyl-benzenesulfonylamino)-N-methoxy-N-methyl-benzamideHCID 178418918HCID 178418918, compoundHCID 178424791HCID 178424791, compoundHCID 178506562HCID 178506562, compound

Product 1

HCID 251710274-Chloro-n-[5-chloro-2-(7h-pyrrolo[2,3-d]pyrimidine-4-carbonyl)-phenyl]-3-trifluoromethyl-benzenesulfonamideYield 67%

Procedure

iPrMgCl (3.84 mL, 7.56 mmol; 1.97 M solution in THF) was added to iodo-pyrrolopyrimidine (0.882 g, 3.6 mmol) in THF (5 mL) at −78° C. After 15 min, it was warmed to room temperature and added 2,6-dimethylphenymagnesium bromide (2.4 mL, 2.4 mmol; 1.0 M solution in diethyl ether). To this reaction mixture at room temperature was added a sodium salt THF solution of 4-chloro-2-(4-chloro-3-trifluoromethyl-benzenesulfonylamino)-N-methoxy-N-methyl-benzamide [prepared separately by adding 60% NaH (0.144 g, 3.6 mmol) in THF (5 mL)] and stirred overnight. Saturated NH4Cl solution (5 mL) was added and extracted with EtOAc (2×50 mL). EtOAc layer was washed with brine (25 mL), dried (Na2SO4) and evaporated. Crude product was purified by column purification (silica gel, 60% EtOAc in hexanes) followed by recrystallization from CH3CN to obtain title compound (1 g) as a crystalline yellow solid in 67% yield. MS (ES) M+H expected 515.0, found 514.9. 1H NMR (CDCl3, 400 MHz): δ 10. 75 (s, 1H), 9.92 (brs., 1H), 8.92 (d, 1H), 8.05 (s, 1H), 7.92 (dd, 1H), 7.81 (m, 2H), 7.58 (m, 1H), 7.45 (dd, 1H), 7.3 (d, 1H), 6.9 (m, 1H).

Workup

  1. customprepared separately
  2. extractionextracted with EtOAc (2×50 mL)
  3. washEtOAc layer was washed with brine (25 mL)
  4. dry with materialdried (Na2SO4)
  5. customevaporated
  6. customCrude product was purified by column purification (silica gel, 60% EtOAc in hexanes)
  7. customfollowed by recrystallization from CH3CN

Sources & evidence

ORD record
ord-0cb1f3d0f8b8401b8a8abdea72cbd86f
Source dataset
uspto-grants-2011_02
Patent number
US07884110B2

Reaction notes

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