Ammonium Chloride → HCID 118022223, compound

HRID 1498850Notes

Reaction equation

HRID 1498850 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5](/[C:8](/[C:16]2[CH:17]=[N:18][C:19]([N:22]3[CH2:27][CH2:26][N:25]([C:28]4[C:33]5=[CH:34][C:35]([C:37]6[CH:38]=[N:39][N:40]([CH3:42])[CH:41]=6)=[CH:36][N:32]5[N:31]=[CH:30][N:29]=4)[CH2:24][CH2:23]3)=[N:20][CH:21]=2)=[N:9]/[S@:10]([C:12]([CH3:15])([CH3:14])[CH3:13])=[O:11])=[CH:4][CH:3]=1.[CH3:43][Mg]Br.[Cl-].[NH4+]>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([NH:9][S@:10]([C:12]([CH3:13])([CH3:14])[CH3:15])=[O:11])([C:16]2[CH:17]=[N:18][C:19]([N:22]3[CH2:27][CH2:26][N:25]([C:28]4[C:33]5=[CH:34][C:35]([C:37]6[CH:38]=[N:39][N:40]([CH3:42])[CH:41]=6)=[CH:36][N:32]5[N:31]=[CH:30][N:29]=4)[CH2:24][CH2:23]3)=[N:20][CH:21]=2)[CH3:43])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 178418573HCID 178418573, compound2×HCID 178480010HCID 178480010, compound

Product 1

HCID 118022223HCID 118022223, compoundYield 61.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

(S,Z)—N-((4-Fluorophenyl)(2-(4-(6-(1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl)piperazin-1-yl)pyrimidin-5-yl)methylene)-2-methylpropane-2-sulfinamide (190 mg, 0.324 mmol) was taken up in THF (3 mL) and cooled to 0° C. Methylmagnesium bromide (3 M solution in diethyl ether, 0.50 mL, 1.500 mmol) was added and the resulting mixture stirred at 0° C. for 45 minutes. Additional methylmagnesium bromide (3 M solution in diethyl ether, 0.10 mL, 0.300 mmol) was added and stirring at 0° C. continued for 20 minutes. Saturated ammonium chloride was added and the products extracted into EtOAc (×2). The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo while loading onto Celite. Purification of the residue by MPLC (0-10% MeOH-EtOAc) gave (S)—N-(1-(4-fluorophenyl)-1-(2-(4-(6-(1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl)piperazin-1-yl)pyrimidin-5-yl)ethyl)-2-methylpropane-2-sulfinamide (120 mg, 0.199 mmol, 61.5% yield) as a yellow solid (mixture of diastereoisomers). MS (ES+) C30H35FN10OS requires: 602. found: 603 [M+H]+.

Workup

  1. stirringstirring at 0° C.
  2. waitcontinued for 20 minutes
  3. extractionthe products extracted into EtOAc (×2)
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification of the residue by MPLC (0-10% MeOH-EtOAc)
  9. customgave

Sources & evidence

ORD record
ord-04cd88458e8c4228b015fe65d49f3a60
Source dataset
uspto-grants-2015_12
Patent number
US09200002B2

Reaction notes

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