Sodium Carbonate → 4-Amino-2-morpholin-4-ylmethyl-thieno[3,2-c]pyridine-7-carboxylic acid amide

HRID 1868307Notes

Reaction equation

HRID 1868307 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:7][N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[S:5][CH:6]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.CC([O-])=O.[K+].[NH2:37][C:38]1C2C=C(Br)SC=2[C:41]([C:48]([NH2:50])=[O:49])=[CH:40][N:39]=1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:37][C:38]1[C:2]2[CH:3]=[C:4]([CH2:7][N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)[S:5][C:6]=2[C:41]([C:48]([NH2:50])=[O:49])=[CH:40][N:39]=1

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 7834974-[(4-Bromothien-2-YL)methyl]morpholineHCID 2733548Bis(pinacolato)diboraneHCID 588407134-Amino-2-Bromothieno[3,2-C]pyridine-7-Carboxamide

Product 1

HCID 690663124-Amino-2-morpholin-4-ylmethyl-thieno[3,2-c]pyridine-7-carboxylic acid amideYield 83.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a mixture of 4-(4-bromo-thiophen-2-ylmethyl)-morpholine 64 (173 mg, 0.66 mmol), bis(pinacolato)diboron (352 mg, 1.39 mmol.), Pd(PPh3)4 (76 mg, 0.07 mmol) and KOAc (194 mg, 2.0 mmol) was added degassed DMF (5 mL). The reaction mixture was heated at 120° C. under N2 for 2 h and then cooled down to room temperature. A solution of 4-amino-2-bromo-thieno[3,2-c]pyridine-7-carboxylic acid amide 17 (150 mg, 0.55 mmol), Pd(PPh3)4 (69 mg, 0.06 mmol) and Na2CO3 (1.0 mL of a 2M aqueous solution, 3.3 mmol) in DMF (2.0 mL) was added. The resulting mixture was heated at 90 0 C for 1.5 h. The solvent was then removed via vacuum, the residue was dissolved in DMSO (4.0 mL) and the mixture purified by reverse phase preparative HPLC to give 66 (134 mg). 1H NMR (400 MHz, CDCl3) δ, 3.12 (m, 2H), 3.32 (m, 2H), 3.82 (m, 2H), 3.95 (m, 2H), 4.62 (s, 2H), 7.75 (s, 1H), 7.81 (br, 1H), 8.09 (s, 1H), 8.34 (s, 1H), 8.38 (br, 1H), 8.56 (s, 1H), 9.19 (br, 1H), 11.73 (br, 1H). MS (EI) m/z (M+H+) 375.

Workup

  1. additionwas added
  2. customdegassed DMF (5 mL)
  3. temperaturecooled down to room temperature
  4. temperatureThe resulting mixture was heated at 90 0 C for 1.5 h
  5. customThe solvent was then removed via vacuum
  6. dissolutionthe residue was dissolved in DMSO (4.0 mL)
  7. customthe mixture purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-396f16b8c3d044f39bb1e21aff86eb2f
Source dataset
uspto-grants-2009_12
Patent number
US07635695B2

Reaction notes

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