Thiazole → HCID 58709960, compound

HRID 2375938Notes

Reaction equation

HRID 2375938 reaction equation
I[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[C:12]3[CH:19]=[C:18]([C:20]4[CH2:21][CH2:22][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:24][CH:25]=4)[NH:17][C:13]=3[N:14]=[CH:15][N:16]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].[S:33]1[CH:37]=[CH:36][N:35]=[CH:34]1.C([O-])(=O)C.[K+]>CN(C=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:9][O:8][C:7]1[CH:6]=[CH:5][C:4]([NH:10][C:11]2[C:12]3[CH:19]=[C:18]([C:20]4[CH2:21][CH2:22][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:24][CH:25]=4)[NH:17][C:13]=3[N:14]=[CH:15][N:16]=2)=[CH:3][C:2]=1[C:37]1[S:33][CH:34]=[N:35][CH:36]=1

Participants

6

Reactant 3

HCID 9256ThiazoleHCID 517044Potassium AcetateHCID 58710073HCID 58710073, compound

Product 1

HCID 58709960HCID 58709960, compound

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

Nitrogen was bubbled through a solution of tert-butyl 4-[4-(3-iodo-4-methoxyphenylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-2H-pyridine-1-carboxylate (109.5 mg, 0.2 mmol), thiazole (85.1 mg, 1.0 mmol), potassium acetate (39.3 mg, 0.4 mmol), and tetrakis(triphenylphosphine)-palladium (23.1 mg, 0.02 mmol) in DMF (0.8 mL) for 3 min. The mixture was then heated to 100° C. and stirred for 17 h. The solvents were removed in vaccuo and the residue was dissolved in DMF (−2 mL). The DMF solution was filtered and sent to mass-directed HPLC purification to give the title compound. 1H-NMR (CD3OD, 400 MHz): δ=1.50 (s, 9H), 2.55 (m, 2H), 3.66 (m, 2H), 3.98 (s, 3H), 4.13 (m, 2H), 6.28 (s, br, 1H), 6.60 (s, 1H), 7.17 (d, J=9.2 Hz, 1H), 7.68 (dd, J=2.4, 8.8 Hz, 1H), 8.06 (d, J=2.8 Hz, 1H), 8.20 (s, 1H), 8.31 (s, 1H), 8.98 (s, 1H). MS (ES+): m/z 504.99 (MH+). HPLC: tR=2.95 min (ZQ2000, polar—5 min). The following EXAMPLES 300-301 are compounds of Formula (I) wherein X=C—CN.

Workup

  1. customThe solvents were removed in vaccuo
  2. dissolutionthe residue was dissolved in DMF (−2 mL)
  3. filtrationThe DMF solution was filtered
  4. customsent to mass-directed HPLC purification

Sources & evidence

ORD record
ord-dbf3ddf0096e4a7488fc83b295b650c0
Source dataset
uspto-grants-2008_12
Patent number
US07465726B2

Reaction notes

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