Water → 3-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-(hydroxymethyl)pyrimidin-2-yl)benzenesulfonamide

HRID 1484863Notes

Reaction equation

HRID 1484863 reaction equation
C([NH:5][S:6]([C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]2[N:20]=[C:19]([NH:21][C:22]3[CH:26]=[C:25]([CH:27]4[CH2:29][CH2:28]4)[NH:24][N:23]=3)[C:18]([CH2:30][O:31][Si](C(C)(C)C)(C)C)=[CH:17][N:16]=2)[CH:10]=1)(=[O:8])=[O:7])(C)(C)C.B(Cl)(Cl)Cl.C(Cl)Cl.O>C(Cl)Cl>[CH:27]1([C:25]2[NH:24][N:23]=[C:22]([NH:21][C:19]3[C:18]([CH2:30][OH:31])=[CH:17][N:16]=[C:15]([C:11]4[CH:10]=[C:9]([S:6]([NH2:5])(=[O:7])=[O:8])[CH:14]=[CH:13][CH:12]=4)[N:20]=3)[CH:26]=2)[CH2:28][CH2:29]1

Participants

5

Reactant 3

HCID 962WaterHCID 20463568Boron trichloride methylene chlorideHCID 58169531N-tert-butyl-3-(5-((tert-butyldimethylsilyloxy)methyl)-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)benzenesulfonamide

Product 1

HCID 581692073-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-(hydroxymethyl)pyrimidin-2-yl)benzenesulfonamideYield 10.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

A mixture of N-tert-butyl-3-(5-((tert-butyldimethylsilyloxy)methyl)-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)benzenesulfonamide (400 mg, 0.718 mmol), BCl3/CH2Cl2 (10 mL, 10 mmol, 13.9 eq, 1 M) in CH2Cl2 (10 mL) was stirred at 20° C. under a nitrogen atmosphere for 30 h. Water (50 mL) was added into the mixture. The mixture was extracted with EtOAc (3×50 mL). The combined organic phases were washed (sat NaHCO3, brine), dried (Na2SO4), filtered and concentrated. The residue was purified by silica gel chromatography (CH2Cl2/MeOH 500:1 to 15:1 as eluent) to afford compound 3-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-(hydroxymethyl)pyrimidin-2-yl)benzenesulfonamide (Compound 124) (28 mg, 10%) as yellowish solid. LC-MS (m/z)=387.1 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 0.81-0.82 (m, 2H), 0.94-0.98 (m, 2H), 1.92-1.95 (m, 1H), 4.61 (d, J=5.2 Hz, 2H), 5.65 (t, J=5.2 Hz, 1H), 6.54 (s, 1H), 7.44 (s, 2H), 7.72 (t, J=8 Hz, 1H), 7.95 (d, J=7.6 Hz, 1H), 8.35 (d, J=5.6 Hz, 1H), 8.51 (d, J=7.6 Hz, 1H), 8.84 (s, 1H), 8.92 (s, 1H), 12.18 (s, 1H).

Workup

  1. extractionThe mixture was extracted with EtOAc (3×50 mL)
  2. washThe combined organic phases were washed (sat NaHCO3, brine)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography (CH2Cl2/MeOH 500:1 to 15:1 as eluent)

Sources & evidence

ORD record
ord-971e3cdc54e2486eaba97ad38f49c222
Source dataset
uspto-grants-2016_08
Patent number
US09422271B2

Reaction notes

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