Nitrogen → 7-[(methyloxy)methyl]-5-{1-[(3-methylphenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7H-pyrrolo[2,3-d]pyrimidin-4-amine

HRID 1910021Notes

Reaction equation

HRID 1910021 reaction equation
Br[C:2]1[C:10]2[C:9]([NH2:11])=[N:8][CH:7]=[N:6][C:5]=2[N:4]([CH2:12][O:13][CH3:14])[CH:3]=1.[CH3:15][C:16]1[CH:17]=[C:18]([CH2:22][C:23]([N:25]2[C:33]3[C:28](=[CH:29][C:30](B4OC(C)(C)C(C)(C)O4)=[CH:31][CH:32]=3)[CH2:27][CH2:26]2)=[O:24])[CH:19]=[CH:20][CH:21]=1.C([O-])(O)=O.[Na+].N#N>O1CCOCC1.O.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>[CH3:14][O:13][CH2:12][N:4]1[C:5]2[N:6]=[CH:7][N:8]=[C:9]([NH2:11])[C:10]=2[C:2]([C:30]2[CH:29]=[C:28]3[C:33](=[CH:32][CH:31]=2)[N:25]([C:23](=[O:24])[CH2:22][C:18]2[CH:19]=[CH:20][CH:21]=[C:16]([CH3:15])[CH:17]=2)[CH2:26][CH2:27]3)=[CH:3]1

Participants

8

Reactant 4

HCID 947NitrogenHCID 516892Sodium BicarbonateHCID 668236285-bromo-7-[(methyloxy)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amineHCID 668241231-[(3-methylphenyl)acetyl]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-indole

Product 1

HCID 534686607-[(methyloxy)methyl]-5-{1-[(3-methylphenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7H-pyrrolo[2,3-d]pyrimidin-4-amineYield 33.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To 5-bromo-7-[(methyloxy)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine (65 mg, 0.253 mmol), and 1-[(3-methylphenyl)acetyl]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-indole (114 mg, 0.303 mmol) were dissolved in 1,4-Dioxane (2 mL) was added saturated NaHCO3 (1 mL). The mixture was then bubbled N2 gas for 10 min then added Pd(Ph3P)4 (29.2 mg, 0.025 mmol) then bubbled for 5 additional minutes. The reaction was then capped and heated at 100° C. overnight. The mixture cooled then diluted with water (10 mL) and extracted with EtOAc (3×20 ml). The organics were combined, washed with brine, dried over MgSo4, filtered and concentrated to afford an amber color oil. The oil was then purified on a 10 g Biotage SNAP column conditioned with Hexane using a gradient of 0 to 10% MeOH in DCM for 30 minutes to isolate 7-[(methyloxy)methyl]-5-{1-[(3-methylphenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7H-pyrrolo[2,3-d]pyrimidin-4-amine (36 mg) as a white solid. LC-MS (ES) m/z=428.4 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 8.17 (s, 1H), 8.15 (d, J=8.34 Hz, 1H), 7.37 (s, 1H), 7.32-7.35 (m, 1H), 7.24 (dd, J=7.33, 14.65 Hz, 2H), 7.06-7.15 (m, 3H), 6.15 (br. s., 2H), 5.50 (s, 2H), 4.21 (s, 2H), 3.83 (s, 2H), 3.25 (s, 3H), 3.19-3.25 (m, 2H), 2.31 (s, 3H).

Workup

  1. customThe reaction was then capped
  2. temperatureThe mixture cooled
  3. extractionextracted with EtOAc (3×20 ml)
  4. washwashed with brine
  5. customdried over MgSo4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford an amber color oil
  9. customThe oil was then purified on a 10 g Biotage SNAP column
  10. customfor 30 minutes

Sources & evidence

ORD record
ord-c547de6ee08848ef9409353767e76a23
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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