Diisopropylethylamine → HCID 86706480, compound

HRID 919623Notes

Reaction equation

HRID 919623 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][CH2:10][C:11]([N:13]2[CH2:22][CH:21]([NH2:23])[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH2:14]2)=[O:12])[CH:5]=[C:6]([Cl:8])[CH:7]=1.Cl[C:25]1[C:26]2[CH:33]=[CH:32][N:31]([S:34]([C:37]3[CH:43]=[CH:42][C:40]([CH3:41])=[CH:39][CH:38]=3)(=[O:36])=[O:35])[C:27]=2[N:28]=[CH:29][N:30]=1.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[Cl:8][C:6]1[CH:5]=[C:4]([NH:9][CH2:10][C:11]([N:13]2[CH2:22][CH:21]([NH:23][C:25]3[C:26]4[CH:33]=[CH:32][N:31]([S:34]([C:37]5[CH:43]=[CH:42][C:40]([CH3:41])=[CH:39][CH:38]=5)(=[O:35])=[O:36])[C:27]=4[N:28]=[CH:29][N:30]=3)[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH2:14]2)=[O:12])[CH:3]=[C:2]([Cl:1])[CH:7]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 442289674-Chloro-7-(p-toluenesulfonyl)-7H-pyrrolo[2,3-d]pyrimidineHCID 67517677HCID 67517677, compound

Product 1

HCID 86706480HCID 86706480, compoundYield 57%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 2-(3,5-dichlorophenylamino)-1-(4-amino-3,4-dihydroisoquinolin-2(1H)-yl)ethanone (0.2 g, 0.6 mmol) in DMF was added 4-chloro-7-tosyl-7H-pyrrolo[2,3-d]pyrimidine (0.17 g, 0.57 mmol) and DIEA (0.11 g, 0.85 mmol). The reaction mixture was stirred at 90° C. overnight, the mixture was diluted with EtOAc (100 mL) and washed with water (20 mL×3). The EtOAc layer was concentrated in vacuo to give a mixture which was purified by column chromatography (silica gel, gradient EtOAc in Hexanes) to give (0.160 g, 57%) of the titled intermediate. 1H NMR (CDCl3, 400 MHz): δ 8.41 (s, 1H), 8.08 (s, 1H), 8.06 (s, 1H), 8.01 (s, 1H), 7.54 (d, 1H, J=3.6 Hz), 7.33-7.19 (m, 6H), 6.83-6.67 (m, 3H), 6.35 (s, 2H), 5.35-5.25 (m, 1H), 5.18 (d, J=16.4 Hz, 1H), 4.76 (d, J=16.4 Hz, 1H), 4.51 (dd, J=1.8, 16 Hz, 1H), 4.33 (t, J=1.8 Hz, 1H), 3.82 (dd, J=1.8, 10 Hz, 1H), 3.72 (d, J=5.2 Hz, 1H), 2.38 (s, 3H). LCMS: M/z: (M+1):621

Workup

  1. washwashed with water (20 mL×3)
  2. concentrationThe EtOAc layer was concentrated in vacuo
  3. customto give a mixture which
  4. customwas purified by column chromatography (silica gel, gradient EtOAc in Hexanes)

Sources & evidence

ORD record
ord-fdf3b64cbc3c4b18b7869376229684c0
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

Loading…