o-Tolylacetic acid → 1-(5-(4-Amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)indolin-1-yl)-2-(o-tolyl)ethan-1-one

HRID 1909958Notes

Reaction equation

HRID 1909958 reaction equation
Cl.Cl.[NH:3]1[C:11]2[C:6](=[CH:7][C:8]([C:12]3[C:20]4[C:19]([NH2:21])=[N:18][CH:17]=[N:16][C:15]=4[N:14]([CH3:22])[CH:13]=3)=[CH:9][CH:10]=2)[CH2:5][CH2:4]1.[CH3:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[CH2:30][C:31](O)=[O:32].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.O.CCOC(C)=O>[CH3:22][N:14]1[C:15]2[N:16]=[CH:17][N:18]=[C:19]([NH2:21])[C:20]=2[C:12]([C:8]2[CH:7]=[C:6]3[C:11](=[CH:10][CH:9]=2)[N:3]([C:31](=[O:32])[CH2:30][C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=2[CH3:23])[CH2:4][CH2:5]3)=[CH:13]1

Participants

8

Reactant 4

HCID 69519o-Tolylacetic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 668234705-(2,3-dihydro-1H-indol-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine dihydrochloride

Product 1

HCID 534694531-(5-(4-Amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)indolin-1-yl)-2-(o-tolyl)ethan-1-oneYield 57.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

In a 20 mL vial with cap, to the solution of 5-(2,3-dihydro-1H-indol-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine-2HCl (70.6 mg, 0.209 mmol), (2-methylphenyl)acetic acid (31.4 mg, 0.209 mmol), HATU (79 mg, 0.209 mmol) in DMF (2 mL) was added Hunig's base (0.146 mL, 0.836 mmol). The mixture was stirred at room temperature overnight. LCMS showed reaction was completed. The reaction was poured into water (100 mL), white solid formed. EtOAc (100 mL) was used to extract the product. The Organic phase was separated from the water phase, dried by MgSO4, rotavaped to dryness, to give white solid. The solid was sonacated in water (10 mL), then filtered and dried to afford 7-methyl-5-{1-[(2-methylphenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7H-pyrrolo[2,3-d]pyrimidin-4-amine (48 mg) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.02-8.24 (m, 2H) 7.32 (s, 1H) 7.25 (s, 1H) 7.12-7.24 (m, 5H) 6.07 (br. s., 2H) 4.26 (t, J=8.5 Hz, 2H) 3.87 (s, 2H) 3.73 (s, 3H) 3.24 (t, J=8.5 Hz, 2H) 2.24 (s, 3H).

Workup

  1. customreaction
  2. customformed
  3. extractionto extract the product
  4. customThe Organic phase was separated from the water phase
  5. dry with materialdried by MgSO4
  6. customto give white solid
  7. filtrationfiltered
  8. customdried

Sources & evidence

ORD record
ord-eb0b76df645e4b12b3d3b1b25be89c01
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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