5-Bromothieno[2,3-D]pyrimidin-4-amine → 5-{1-[(3-methylphenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}thieno[2,3-d]pyrimidin-4-amine

HRID 1909988Notes

Reaction equation

HRID 1909988 reaction equation
Br[C:2]1[C:10]2[C:9]([NH2:11])=[N:8][CH:7]=[N:6][C:5]=2[S:4][CH:3]=1.[CH3:12][C:13]1[CH:14]=[C:15]([CH2:19][C:20]([N:22]2[C:30]3[C:25](=[CH:26][C:27](B4OC(C)(C)C(C)(C)O4)=[CH:28][CH:29]=3)[CH2:24][CH2:23]2)=[O:21])[CH:16]=[CH:17][CH:18]=1>O1CCOCC1.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(Cl)Cl>[CH3:12][C:13]1[CH:14]=[C:15]([CH2:19][C:20]([N:22]2[C:30]3[C:25](=[CH:26][C:27]([C:2]4[C:10]5[C:9]([NH2:11])=[N:8][CH:7]=[N:6][C:5]=5[S:4][CH:3]=4)=[CH:28][CH:29]=3)[CH2:24][CH2:23]2)=[O:21])[CH:16]=[CH:17][CH:18]=1

Participants

6

Reactant 2

HCID 668238985-Bromothieno[2,3-D]pyrimidin-4-amineHCID 66824123HCID 66824123, compound

Product 1

HCID 668236735-{1-[(3-methylphenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}thieno[2,3-d]pyrimidin-4-amineYield 76%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 5-bromothieno[2,3-d]pyrimidin-4-amine (90 mg, 0.391 mmol) and 1-[(3-methylphenyl)acetyl]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-indole (148 mg, 0.391 mmol) in 1,4-Dioxane (6 mL) and sat. aq. NaHCO3 (2 mL) was degassed with N2 for 10 minutes. PdCl2(dppf)-CH2Cl2 adduct (15.97 mg, 0.020 mmol) was added, and the reaction mixture was stirred overnight at 100° C. in a sealed vessel. The reaction was cooled down to room temperature and poured onto water. The aqueous mixture was filtered, and the solid in the filter was purified via flash chromatography on SiO2 (gradient: 100% Hexanes to 100% EtOAc) to afford the desired product (119 mg) as a white solid. LC-MS (ES) m/z=401.3 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 2.31 (s, 3H), 3.22 (t, J=8.46 Hz, 2H), 3.84 (s, 2H), 4.23 (t, J=8.46 Hz, 2H), 7.04-7.16 (m, 3H), 7.20-7.29 (m, 2H), 7.34 (s, 1H), 7.42 (s, 1H), 8.17 (d, J=8.34 Hz, 1H), 8.34 (s, 1H).

Workup

  1. customwas degassed with N2 for 10 minutes
  2. temperatureThe reaction was cooled down to room temperature
  3. additionpoured onto water
  4. filtrationThe aqueous mixture was filtered
  5. customthe solid in the filter was purified via flash chromatography on SiO2 (gradient: 100% Hexanes to 100% EtOAc)

Sources & evidence

ORD record
ord-7d6bb7296de84d68b5ecfcba20127b47
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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