Hydrochloric Acid → HCID 49785344, compound

HRID 1812343Notes

Reaction equation

HRID 1812343 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([NH:9][S:10]([CH3:13])(=[O:12])=[O:11])[C:5]([Cl:8])=[N:6][CH:7]=1.F[C:15]1[C:20]([C:21]2[N:26]=[C:25]([CH3:27])[N:24]=[C:23]([NH2:28])[N:22]=2)=[CH:19][C:18]([CH:29]2[CH2:34][CH2:33][O:32][CH2:31][CH2:30]2)=[CH:17][N:16]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Cl>CN(C=O)C.O>[NH2:28][C:23]1[N:24]=[C:25]([CH3:27])[N:26]=[C:21]([C:20]2[C:15]([NH:1][C:2]3[CH:3]=[C:4]([NH:9][S:10]([CH3:13])(=[O:12])=[O:11])[C:5]([Cl:8])=[N:6][CH:7]=3)=[N:16][CH:17]=[C:18]([CH:29]3[CH2:30][CH2:31][O:32][CH2:33][CH2:34]3)[CH:19]=2)[N:22]=1

Participants

7

Reactant 4

HCID 313Hydrochloric Acid2×HCID 2724254Sodium bis(trimethylsilyl)amideHCID 66612026HCID 66612026, compoundHCID 71480920N-(5-amino-2-chloro-3-pyridinyl)methanesulfonamide

Product 1

HCID 49785344HCID 49785344, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of N-(5-amino-2-chloropyridin-3-yl)methanesulfonamide (60 mg, 0.271 mmol) and 4-(2-fluoro-5-(tetrahydro-2H-pyran-4-yl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (55 mg, 0.190 mmol) in anhydrous DMF (1 mL) cooled in an ice bath was added solid NaHMDS (210 mg, 1.088 mmol) under nitrogen. The resulting orange mixture was stirred with cooling. After 1.5 h, HCl (5 N, 0.25 mL, 1.25 mmol) was added to the mixture. The resulting mixutre was diluted with water (5 mL) and acidified with HCl, 5 N) to about pH 5. The resulting slurry was filtered and washed with water (3×3 mL). The solid was washed with EtOAc to afford the product as a brown solid. The mother liquid was chromatographed on silica gel (0-5% MeOH in EtOAc) to give additional product. The combined product was about 30 mg (32%). m/z (ESI, positive ion): 491.1 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.60-1.82 (m, 4H) 2.46 (s, 3H) 2.84 (t, J=11.35 Hz, 1H) 3.12 (s, 3H) 3.46 (t, J=10.76 Hz, 2H) 3.97 (d, J=12.13 Hz, 2H) 7.78 (br. s., 1H) 7.92 (br. s., 1H) 8.33 (s, 1H) 8.64 (d, J=3.33 Hz, 2H) 8.72 (s, 1H) 9.64 (br. s., 1H) 12.17 (s, 1H).

Workup

  1. temperaturewith cooling
  2. filtrationThe resulting slurry was filtered
  3. washwashed with water (3×3 mL)
  4. washThe solid was washed with EtOAc

Sources & evidence

ORD record
ord-f497e77d00d649e1a518069b99c10312
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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