Methanesulfonyl chloride → HCID 123177998, compound

HRID 60657Notes

Reaction equation

HRID 60657 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([NH:29][C:30]([NH:32][C@@H:33]2[C:42]3[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=3)[C@H:36]([O:43][C:44]3[CH:45]=[CH:46][C:47]4[N:48]([C:50]([N:53]5[CH2:58][CH2:57][CH2:56][CH2:55][C@@H:54]5[CH3:59])=[N:51][N:52]=4)[CH:49]=3)[CH2:35][CH2:34]2)=[O:31])[N:8]([C:10]2[CH:15]=[CH:14][C:13]([O:16][Si:17]([CH:24]([CH3:26])[CH3:25])([CH:21]([CH3:23])[CH3:22])[CH:18]([CH3:20])[CH3:19])=[C:12]([CH2:27]O)[CH:11]=2)[N:9]=1)([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.CS([Cl:73])(=O)=O.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[C:1]([C:5]1[CH:6]=[C:7]([NH:29][C:30]([NH:32][C@@H:33]2[C:42]3[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=3)[C@H:36]([O:43][C:44]3[CH:45]=[CH:46][C:47]4[N:48]([C:50]([N:53]5[CH2:58][CH2:57][CH2:56][CH2:55][C@@H:54]5[CH3:59])=[N:51][N:52]=4)[CH:49]=3)[CH2:35][CH2:34]2)=[O:31])[N:8]([C:10]2[CH:15]=[CH:14][C:13]([O:16][Si:17]([CH:24]([CH3:26])[CH3:25])([CH:21]([CH3:23])[CH3:22])[CH:18]([CH3:20])[CH3:19])=[C:12]([CH2:27][Cl:73])[CH:11]=2)[N:9]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 31297Methanesulfonyl chloride2×HCID 81531Diisopropylethylamine2×HCID 516892Sodium BicarbonateHCID 1233790051-[5-tert-Butyl-2-(3-hydroxymethyl-4-triisopropylsilanyloxy-phenyl)-2H-pyrazol-3-yl]-3-((1S,4R)-4-[3-((S)-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea

Product 1

HCID 123177998HCID 123177998, compoundYield 27%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of Intermediate 61e (124 mg, 0.15 mmol) in DCM (1.5 mL) at 0° C. was treated with DIPEA (79 μL, 0.45 mmol) then methanesulfonyl chloride (23 μL, 0.30 mmol) and the mixture was stirred at RT for 1 h. The mixture was cooled to 0° C. and treated with another portion of DIPEA (40 μL, 0.23 mmol) and methanesulfonyl chloride (12 μL, 0.15 mmol) and stirred at RT for 30 min. The mixture was diluted with DCM and a saturated aqueous sodium bicarbonate solution. The layers were separated and the aqueous layer was then extracted with DCM (2×). The combined organic layers were washed with water, a saturated aqueous sodium bicarbonate solution and brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by FCC, using 0-4% MeOH in DCM, to give the title compound (34 mg, 27%). LCMS (Method 3): Rt 5.56 min, m/z 839 [MH+].

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was then extracted with DCM (2×)
  3. washThe combined organic layers were washed with water
  4. dry with materiala saturated aqueous sodium bicarbonate solution and brine, dried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-c4561dd30f614c4791bb201b6d5888cb
Source dataset
uspto-grants-2016_09
Patent number
US09440974B2

Reaction notes

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