Potassium Hydroxide → HCID 178485534, compound

HRID 1014447Notes

Reaction equation

HRID 1014447 reaction equation
[CH3:1][N:2]([CH3:49])[CH2:3][C:4]([N:6]1[C:14]2[C:9](=[CH:10][C:11]([O:47][CH3:48])=[C:12]([NH:15][C:16]3[N:17]=[C:18]([NH:35][C:36]4[CH:45]=[CH:44][CH:43]=[C:42]([F:46])[C:37]=4[C:38]([NH:40][CH3:41])=[O:39])[C:19]4[CH:24]=[CH:23][N:22](S(C5C=CC(C)=CC=5)(=O)=O)[C:20]=4[N:21]=3)[CH:13]=2)[CH2:8][CH2:7]1)=[O:5].[OH-].[K+]>O1CCOCC1>[OH2:5].[CH3:49][N:2]([CH3:1])[CH2:3][C:4]([N:6]1[C:14]2[C:9](=[CH:10][C:11]([O:47][CH3:48])=[C:12]([NH:15][C:16]3[NH:21][C:20]4=[N:22][CH:23]=[CH:24][C:19]4=[C:18]([NH:35][C:36]4[CH:45]=[CH:44][CH:43]=[C:42]([F:46])[C:37]=4[C:38]([NH:40][CH3:41])=[O:39])[N:17]=3)[CH:13]=2)[CH2:8][CH2:7]1)=[O:5]

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 59442024HCID 59442024, compound

Product 1

HCID 178485534HCID 178485534, compoundYield 184.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

A light brown solution of 2-({2-{[1-(N,N-dimethylglycyl)-5-(methoxy)-2,3-dihydro-1H-indol-6-yl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluoro-N-methylbenzamide (19.1 kg, 27.8 mol), a method for preparation of which is described in Step C above, was suspended in dioxane (191 L, 10 volumes) and treated with a 15% aqueous KOH solution (76.4 L, 4 volumes). The mixture was heated to reflux (approximately 85° C.). Once the suspension became homogeneous, the reaction mixture was kept at reflux for 2 hours. In-process monitoring after 2 h showed completion. The heat was discontinued and the suspension was concentrated to remove approximately 80 L of solvent. Water (141 L) was added and the suspension was stirred at ambient temperature for 1 h and filtered through centrifuge. The solid was washed with water till the filtrate ran clear to obtain 2-[(2-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-6-fluoro-N-methylbenzamide monohydrate as a light brown solid (14.1 kg, 95% yield).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 2 hours
  3. concentrationthe suspension was concentrated
  4. customto remove approximately 80 L of solvent
  5. additionWater (141 L) was added
  6. filtrationfiltered through centrifuge
  7. washThe solid was washed with water till the filtrate

Sources & evidence

ORD record
ord-e67dafcd5eeb45e097e924323aae361c
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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