2-Bromothiazole → N,N-dicyclopropyl-6-ethyl-1-methyl-4-(thiazol-2-ylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide

HRID 220348Notes

Reaction equation

HRID 220348 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]2[N:8]([CH2:20][CH3:21])[C:9]([C:11]([N:13]([CH:17]3[CH2:19][CH2:18]3)[CH:14]3[CH2:16][CH2:15]3)=[O:12])=[CH:10][C:5]2=[C:4]2[N:22]([CH3:25])[CH:23]=[N:24][C:3]=12.Br[C:27]1[S:28][CH:29]=[CH:30][N:31]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[CH:14]1([N:13]([CH:17]2[CH2:19][CH2:18]2)[C:11]([C:9]2[N:8]([CH2:20][CH3:21])[C:6]3=[N:7][C:2]([NH:1][C:27]4[S:28][CH:29]=[CH:30][N:31]=4)=[C:3]4[N:24]=[CH:23][N:22]([CH3:25])[C:4]4=[C:5]3[CH:10]=2)=[O:12])[CH2:16][CH2:15]1

Participants

7

Reactant 4

HCID 764302-BromothiazoleHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 581805034-amino-N,N-dicyclopropyl-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide

Product 1

HCID 58180628N,N-dicyclopropyl-6-ethyl-1-methyl-4-(thiazol-2-ylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamideYield 10.7%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
85 °C

Procedure

To a mixture of 4-amino-N,N-dicyclopropyl-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (example 1J, 30 mg, 0.089 mmol), 2-bromothiazole (11.98 μL, 0.133 mmol), Pd2(dba)3 (12.18 mg, 0.013 mmol), BINAP (24.84 mg, 0.040 mmol) and sodium tert-butoxide (13.63 mg, 0.142 mmol) was added PhMe (887 μL). The mixture was sparged with argon gas for 5 min and heated to 85° C. for 5.5 h. The reaction mixture was filtered through a plug of Celite and concentrated. The crude residue was purified by preparative HPLC to provide N,N-dicyclopropyl-6-ethyl-1-methyl-4-(thiazol-2-ylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (4 mg, 10.49% yield) along with some recovered starting material.

Workup

  1. customThe mixture was sparged with argon gas for 5 min
  2. filtrationThe reaction mixture was filtered through a plug of Celite
  3. concentrationconcentrated
  4. customThe crude residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-78082e737b474b0e9e5f1810ac4e8368
Source dataset
uspto-grants-2012_06
Patent number
US08202881B2

Reaction notes

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