Sodium Bicarbonate → 2-cyano-2-{6-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-pyrimidin-4-yl}-N,N-dimethyl-acetamide

HRID 886556Notes

Reaction equation

HRID 886556 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15](B3OC(C)(C)C(C)(C)O3)[CH:16]=2)[N:11]([S:27]([C:30]2[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=2)(=[O:29])=[O:28])[CH:10]=1.Cl[C:38]1[N:43]=[CH:42][N:41]=[C:40]([CH:44]([C:50]#[N:51])[C:45]([N:47]([CH3:49])[CH3:48])=[O:46])[CH:39]=1.C(=O)(O)[O-].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(#N)C>[C:50]([CH:44]([C:40]1[CH:39]=[C:38]([C:15]2[CH:16]=[C:17]3[C:9]([C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[O:2][CH3:1])=[CH:10][N:11]([S:27]([C:30]4[CH:31]=[CH:32][C:33]([CH3:36])=[CH:34][CH:35]=4)(=[O:28])=[O:29])[C:12]3=[N:13][CH:14]=2)[N:43]=[CH:42][N:41]=1)[C:45]([N:47]([CH3:49])[CH3:48])=[O:46])#[N:51]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 160390673-(2-Methoxyphenyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridineHCID 866239462-(6-Chloro-pyrimidin-4-yl)-2-cyano-N,N-dimethyl-acetamide

Product 1

HCID 598249952-cyano-2-{6-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-pyrimidin-4-yl}-N,N-dimethyl-acetamideYield 68%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 3-(2-Methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine (1.0 g, 2.0 mmole), 2-(6-Chloro-pyrimidin-4-yl)-2-cyano-N,N-dimethyl-acetamide (prepared according to the method published in Tetrahedron Letters (2005) 46, 3587-3589) (670 mg, 3.0 mmole), sodium bicarbonate, (2M aq, 4.9 mmole), acetonitrile (13.2 mL), and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (97 mg, 0.12 mmole) was heated in a microwave reactor at 120° C. for 45 min. The crude mixture was concentrated to dryness, suspended in water (50 mL), and stirred for 30 min. The resulting precipitate was filtered off, suspended in ethyl acetate (15 mL), and stirred for 15 h. The precipitate was filtered off, rinsed with ethyl acetate (3×5 mL), and air dried. Recrystallization from ethylacetate/methanol afforded 2-cyano-2-{6-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-pyrimidin-4-yl}-N,N-dimethyl-acetamide (762 mg, 68% yield) as a bright yellow solid. MS: m/z 567.1 (M+H+).

Workup

  1. customprepared
  2. concentrationThe crude mixture was concentrated to dryness
  3. filtrationThe resulting precipitate was filtered off
  4. stirringstirred for 15 h
  5. filtrationThe precipitate was filtered off
  6. washrinsed with ethyl acetate (3×5 mL), and air
  7. customdried
  8. customRecrystallization from ethylacetate/methanol

Sources & evidence

ORD record
ord-2a77cb2b64db4689b2c3e471865c7f28
Source dataset
uspto-grants-2012_08
Patent number
US08242280B2

Reaction notes

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