4-Chloro-2-fluorobenzene-1-sulfonyl chloride → 4-chloro-2-fluoro-N-(5-(4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)benzene-sulfonamide

HRID 1182970Notes

Reaction equation

HRID 1182970 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([O:7][C:8]2[C:9]3[N:17]=[C:16]([C:18]4[CH:19]=[C:20]([NH2:24])[CH:21]=[N:22][CH:23]=4)[CH:15]=[CH:14][C:10]=3[N:11]=[CH:12][N:13]=2)[CH2:3][CH2:2]1.[Cl:25][C:26]1[CH:31]=[CH:30][C:29]([S:32](Cl)(=[O:34])=[O:33])=[C:28]([F:36])[CH:27]=1>N1C=CC=CC=1.C(Cl)Cl>[Cl:25][C:26]1[CH:31]=[CH:30][C:29]([S:32]([NH:24][C:20]2[CH:21]=[N:22][CH:23]=[C:18]([C:16]3[CH:15]=[CH:14][C:10]4[N:11]=[CH:12][N:13]=[C:8]([O:7][CH:4]5[CH2:5][CH2:6][O:1][CH2:2][CH2:3]5)[C:9]=4[N:17]=3)[CH:19]=2)(=[O:33])=[O:34])=[C:28]([F:36])[CH:27]=1

Participants

5

Reactant 2

HCID 27788604-Chloro-2-fluorobenzene-1-sulfonyl chlorideHCID 682288595-(4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-amine2×

Product 1

HCID 665582094-chloro-2-fluoro-N-(5-(4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)benzene-sulfonamideYield 43%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-(4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-amine (Intermediate 12) (0.050 g, 0.155 mmol) in pyridine (0.773 ml) was slowly added 4-chloro-2-fluorobenzene-1-sulfonyl chloride (0.043 g, 0.186 mmol) at 0° C. After stirred for 1 hour at room temperature, the reaction mixture was diluted with DCM and quenched with 1N. aq HCl. The combined organic layers were washed brine, dried over anhydrous MgSO4, filtered and concentrated in vacuo. The residue was recrystallized from EtOAc-Hexane to give 4-chloro-2-fluoro-N-(5-(4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)benzene-sulfonamide (0.034 g, 43%) as a purple solid. 1H-NMR (CDCl3, Varian 400 MHz) δ 2.03-2.11 (2H, m), 2.23-2.28 (2H, m), 3.70-3.75 (2H, m), 4.11-4.16 (2H, m), 5.65-5.71 (1H, m), 7.24 (1H, d, J=8.4 Hz), 7.86-7.90 (1H, m), 8.24 (1H, d, J=8.8 Hz), 8.39 (1H, d, J=8.8 Hz), 8.66 (1H, d, J=7.6 Hz), 8.85 (1H, s), 9.19 (1H, s). m/z=516.1 [M+1]+.

Workup

  1. customat 0° C
  2. customquenched with 1N
  3. washThe combined organic layers were washed brine
  4. dry with materialdried over anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was recrystallized from EtOAc-Hexane

Sources & evidence

ORD record
ord-5a88ade3373342fea3088713b225950a
Source dataset
uspto-grants-2014_03
Patent number
US08664230B2

Reaction notes

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