Potassium Hydroxide → HCID 178493018, compound

HRID 1014438Notes

Reaction equation

HRID 1014438 reaction equation
[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]([NH:12][C:13]2[C:14]3[CH:39]=[CH:38][N:37](S(C4C=CC(C)=CC=4)(=O)=O)[C:15]=3[N:16]=[C:17]([NH:19][C:20]3[CH:25]=[CH:24][C:23]([N:26]4[CH2:31][CH2:30][N:29]([CH:32]([CH3:34])[CH3:33])[CH2:28][CH2:27]4)=[CH:22][C:21]=3[O:35][CH3:36])[N:18]=2)[C:3]=1[C:4]([NH2:6])=[O:5].[OH-].[K+]>O1CCOCC1.CC(O)C.C(OCC)(=O)C>[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]([NH:12][C:13]2[N:18]=[C:17]([NH:19][C:20]3[CH:25]=[CH:24][C:23]([N:26]4[CH2:27][CH2:28][N:29]([CH:32]([CH3:33])[CH3:34])[CH2:30][CH2:31]4)=[CH:22][C:21]=3[O:35][CH3:36])[NH:16][C:15]3=[N:37][CH:38]=[CH:39][C:14]=23)[C:3]=1[C:4]([NH2:6])=[O:5]

Participants

6

Reactant 2

HCID 14797Potassium HydroxideHCID 673173812,4-difluoro-6-({2-{[4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)phenyl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)benzamide

Product 1

HCID 178493018HCID 178493018, compoundYield 86%

Reagents, catalysts & solvents 3

HCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 2,4-difluoro-6-({2-{[4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)phenyl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)benzamide (1.5 g, 2.17 mmols) in 1,4-dioxane (100 ml) and 2-propanol (2 ml) was added 1.0M potassium hydroxide (21 ml, 21.7 mmol) and the reaction was heated at 80C overnight. The resulting solution was diluted with ethyl acetate, washed with water, adsorbed onto silica gel and purified by LC (DCM to 10% MeOH/DCM) to afford 2,4-difluoro-6-[(2-{[4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)phenyl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]benzamide (1.0 g, 86%). ESIMS (M+H)+=537. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.00 (d, J=6.60 Hz, 6H) 2.54-2.60 (m, 4H) 2.64-2.72 (m, 1H) 3.05-3.11(m, 4H) 3.78 (s, 3H) 6.18 (dd, J=3.48, 2.02 Hz, 1H) 6.45 (dd, J=8.62, 2.38 Hz, 1H) 6.61 (d, J=2.57 Hz, 1H) 6.86-6.92 (m, 1H) 6.96 (dd, J=3.67, 2.20 Hz, 1H) 7.59 (s, 1H) 7.68 (d, J=8.80 Hz, 1H) 8.01 (br. s., 1H) 8.16 (s, 1H) 8.53-8.59 (m, 1H) 11.08 (s, 1H) 11.32 (s, 1H).

Workup

  1. washwashed with water
  2. custompurified by LC (DCM to 10% MeOH/DCM)

Sources & evidence

ORD record
ord-f9178f690c594595ab05df768ff09d88
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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