Diisopropylethylamine → 5-{4-chloro-1-[(6-methyl-2-pyridinyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine

HRID 1910100Notes

Reaction equation

HRID 1910100 reaction equation
Cl.Cl.[Cl:3][C:4]1[C:12]([C:13]2[C:21]3[C:20]([NH2:22])=[N:19][CH:18]=[N:17][C:16]=3[N:15]([CH3:23])[CH:14]=2)=[CH:11][CH:10]=[C:9]2[C:5]=1[CH2:6][CH2:7][NH:8]2.OC(C(F)(F)F)=O.[CH3:31][C:32]1[N:37]=[C:36]([CH2:38][C:39](O)=[O:40])[CH:35]=[CH:34][CH:33]=1.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)C=O.O>[Cl:3][C:4]1[C:12]([C:13]2[C:21]3[C:20]([NH2:22])=[N:19][CH:18]=[N:17][C:16]=3[N:15]([CH3:23])[CH:14]=2)=[CH:11][CH:10]=[C:9]2[C:5]=1[CH2:6][CH2:7][N:8]2[C:39](=[O:40])[CH2:38][C:36]1[CH:35]=[CH:34][CH:33]=[C:32]([CH3:31])[N:37]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 668235055-(4-chloro-2,3-dihydro-1H-indol-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine 2HClHCID 66823699(6-methyl-2-pyridinyl)acetic acid TFA salt

Product 1

HCID 534692615-{4-chloro-1-[(6-methyl-2-pyridinyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amineYield 41.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-(4-chloro-2,3-dihydro-1H-indol-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine 2HCl (300 mg, 0.805 mmol), (6-methyl-2-pyridinyl)acetic acid TFA salt (213 mg, 0.805 mmol), HATU (306 mg, 0.805 mmol), in N,N-Dimethylformamide (DMF) (50 mL) under nitrogen at 0° C. was added DIEA (0.562 mL, 3.22 mmol). The reaction was stirred overnight at room temperature, then poured into water and stirred for one hour. A brown precipitate formed which was collected by filtration and washed with water. The solid was dissolved in ca. 25 mL chloroform, and purified by flash chromatography (0-100% EtOAc in chloroform→0-10% MeOH in EtOAc, 24-g column) to afford 5-{4-chloro-1-[(6-methyl-2-pyridinyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (144 mg) as a yellow solid. LC-MS (ES) m/z=433 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.45 (s, 3H), 3.24 (t, J=8.46 Hz, 2H), 3.74 (s, 3H), 4.00 (s, 2H), 4.35 (t, J=8.46 Hz, 2H), 5.69-6.08 (m, 2H), 7.16 (t, J=6.82 Hz, 2H), 7.20-7.25 (m, 2H), 7.66 (t, J=7.58 Hz, 1H), 8.03 (d, J=8.34 Hz, 1H), 8.13 (s, 1H).

Workup

  1. stirringstirred for one hour
  2. customA brown precipitate formed which
  3. filtrationwas collected by filtration
  4. washwashed with water
  5. dissolutionThe solid was dissolved in ca. 25 mL chloroform
  6. custompurified by flash chromatography (0-100% EtOAc in chloroform→0-10% MeOH in EtOAc, 24-g column)

Sources & evidence

ORD record
ord-75a5273430514ea88ba924d2b2889b65
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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