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

HRID 220372Notes

Reaction equation

HRID 220372 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.Cl[C:27]1[S:28][C:29]([C:32]#[N:33])=[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].COCCOC>[C:32]([C:29]1[S:28][C:27]([NH:1][C:2]2[N:7]=[C:6]3[N:8]([CH2:20][CH3:21])[C:9]([C:11]([N:13]([CH:17]4[CH2:19][CH2:18]4)[CH:14]4[CH2:16][CH2:15]4)=[O:12])=[CH:10][C:5]3=[C:4]3[N:22]([CH3:25])[CH:23]=[N:24][C:3]=23)=[N:31][CH:30]=1)#[N:33]

Participants

7

Reactant 4

HCID 634876Binap, (A+-)-HCID 14852222-Chlorothiazole-5-carbonitrileHCID 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 581805324-(5-cyanothiazol-2-ylamino)-N,N-dicyclopropyl-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 80711,2-DimethoxyethaneSolvent

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, 60 mg, 0.177 mmol), 2-chlorothiazole-5-carbonitrile (38.5 mg, 0.266 mmol), Pd2(dba)3 (24.4 mg, 0.027 mmol), BINAP (49.7 mg, 0.080 mmol) and sodium tert-butoxide (27.3 mg, 0.284 mmol) was added DME (1 ml). The mixture was purged with argon gas for 5 min and heated to 85° C. for 3 h. The reaction mixture showed ˜60% conversion by HPLC and was filtered through a plug of Celite and concentrated. The crude product was purified by preparative HPLC to afford 4-(5-cyanothiazol-2-ylamino)-N,N-dicyclopropyl-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide as a off-white solid.

Workup

  1. customThe mixture was purged with argon gas for 5 min
  2. filtrationwas filtered through a plug of Celite
  3. concentrationconcentrated
  4. customThe crude product was purified by preparative HPLC

Sources & evidence

ORD record
ord-dc340c347970467e8433891cf7d0af4c
Source dataset
uspto-grants-2012_06
Patent number
US08202881B2

Reaction notes

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