Methyl iodide → 5-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-(1-methyl-4-piperidinyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

HRID 1909996Notes

Reaction equation

HRID 1909996 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH2:9][C:10]([N:12]1[C:20]2[C:15](=[CH:16][C:17]([C:21]3[C:29]4[C:28]([NH2:30])=[N:27][CH:26]=[N:25][C:24]=4[N:23]([CH:31]4[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]4)[CH:22]=3)=[CH:18][CH:19]=2)[CH2:14][CH2:13]1)=[O:11].[C:37](=O)([O-])[O-].[Cs+].[Cs+].IC>CN(C)C=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH2:9][C:10]([N:12]1[C:20]2[C:15](=[CH:16][C:17]([C:21]3[C:29]4[C:28]([NH2:30])=[N:27][CH:26]=[N:25][C:24]=4[N:23]([CH:31]4[CH2:32][CH2:33][N:34]([CH3:37])[CH2:35][CH2:36]4)[CH:22]=3)=[CH:18][CH:19]=2)[CH2:14][CH2:13]1)=[O:11]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 10796Cesium carbonateHCID 668236445-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-(4-piperidinyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Product 1

HCID 668235635-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-(1-methyl-4-piperidinyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amineYield 18.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 5-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-(4-piperidinyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (85 mg, 0.174 mmol) was added N,N-Dimethylformamide (DMF) (2 mL) and cesium carbonate (170 mg, 0.522 mmol). The mixture was then added iodomethane (0.014 mL, 0.226 mmol) and the reaction was let stir at room temp overnight. The reaction was then filtered using the syringe filter and the filtrate was then diluted with water (20 ml) then extracted with EtOAc (3×15 ml). The organics were combined, washed with brine, dried over MgSO4, filtered, concentrated and then loaded on to a 10 g Biotage SNAP column. Elution with 0 to 10% MeOH in DCM over 30 min gradient afforded 5-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-(1-methyl-4-piperidinyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (16 mg, 0.032 mmol, 18.30% yield) as a white solid. LC/MS (ES) m/z=503.4 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 8.13 (s, 1H), 8.08 (d, J=8.08 Hz, 1H), 7.40 (s, 1H), 7.36 (s, 1H), 7.15-7.30 (m, 4H), 4.56 (d, J=3.54 Hz, 1H), 4.29 (t, J=8.46 Hz, 2H), 3.95 (s, 2H), 3.27 (t, J=8.46 Hz, 2H), 2.93 (br. s., 2H), 2.27 (s, 3H), 2.04-2.18 (m, 4H), 1.85-1.93 (m, 2H). NHs not observed.

Workup

  1. filtrationThe reaction was then filtered
  2. filtrationfilter
  3. additionthe filtrate was then diluted with water (20 ml)
  4. extractionthen extracted with EtOAc (3×15 ml)
  5. washwashed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. washElution with 0 to 10% MeOH in DCM over 30 min

Sources & evidence

ORD record
ord-3794fd10b27e4120b576f06c9a54312a
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

Loading…