2H-1-Benzazepin-2-one, 8-amino-1-ethyl-1,3,4,5-tetrahydro- → 2-[5-Chloro-2-(1-ethyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-8-ylamino)-pyrimidin-4-ylamino]-3,N-dimethyl-benzamide

HRID 1687161Notes

Reaction equation

HRID 1687161 reaction equation
[NH2:1][C:2]1[CH:15]=[CH:14][C:5]2[CH2:6][CH2:7][CH2:8][C:9](=[O:13])[N:10]([CH2:11][CH3:12])[C:4]=2[CH:3]=1.Cl[C:17]1[N:22]=[C:21]([NH:23][C:24]2[C:33]([CH3:34])=[CH:32][CH:31]=[CH:30][C:25]=2[C:26]([NH:28][CH3:29])=[O:27])[C:20]([Cl:35])=[CH:19][N:18]=1>C(O)(C)C>[Cl:35][C:20]1[C:21]([NH:23][C:24]2[C:33]([CH3:34])=[CH:32][CH:31]=[CH:30][C:25]=2[C:26]([NH:28][CH3:29])=[O:27])=[N:22][C:17]([NH:1][C:2]2[CH:15]=[CH:14][C:5]3[CH2:6][CH2:7][CH2:8][C:9](=[O:13])[N:10]([CH2:11][CH3:12])[C:4]=3[CH:3]=2)=[N:18][CH:19]=1

Participants

4

Reactant 2

HCID 98991662H-1-Benzazepin-2-one, 8-amino-1-ethyl-1,3,4,5-tetrahydro-HCID 866338742-(2,5-dichloropyrimidin-4-ylamino)-N,3-dimethylbenzamide

Product 1

HCID 668299372-[5-Chloro-2-(1-ethyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-8-ylamino)-pyrimidin-4-ylamino]-3,N-dimethyl-benzamideYield 57%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
120 °C

Procedure

A microwave vessel was charged with 8-amino-1-ethyl-1,3,4,5-tetrahydro-1-benzazepin-2-one (44.7 mg, 0.219 mmol), 2-(2,5-Dichloro-pyrimidin-4-ylamino)-3,N-dimethyl-benzamide (56.8 mg, 0.182 mmol) 10-camphorsulfonic acid (4.2 mg, 0.018 mmol) and isopropyl alcohol (2.0 mL) and heated in a microwave at 120° C. for 60 minutes. The reaction mixture was quenched with a slurry of saturated, aqueous, NaHCO3 and stirred for 2 h. This mixture was diluted with water (10 mL) and extracted into DCM. The organic layer was dried by passing through a funnel filled with Na2SO4, and the filtrate was evaporated onto celite prior to purification by chromatography (amine modified silica gel, 25% EtOAc/hexane→80% EtOAc gradient). The appropriate fractions were combined, evaporated to afford a solid that was triturated with ether (2×2 mL) and yielded product (49.5 mg, 57%) as a white powder that had the following properties: m.p: 210-212° C.; LC/MS (ESI+): 479 (M+H); 1H-NMR (DMSO-d6, 400 MHz): δ 9.29-9.20 (m, 2H), 8.30 (m, 1H), 8.14 (s, 1H), 7.48-7.40 (m, 2H), 7.36 (d, J=8.3, 1H), 7.29-7.20 (m, 2H), 6.93 (d, J=8.3, 1H), 3.55 (br s, 2H), 2.70 (d, J=4.1, 3H), 2.50 (m, 2H), 2.15 (s, 3H), 2.10-1.85 (m, 4H), 0.92 (t, J=7.0, 3H).

Workup

  1. customThe reaction mixture was quenched with a slurry of saturated, aqueous, NaHCO3
  2. additionThis mixture was diluted with water (10 mL)
  3. extractionextracted into DCM
  4. customThe organic layer was dried
  5. customby passing through a funnel
  6. additionfilled with Na2SO4
  7. customthe filtrate was evaporated onto celite
  8. customto purification by chromatography (amine modified silica gel, 25% EtOAc/hexane→80% EtOAc gradient)
  9. customevaporated
  10. customto afford a solid
  11. customthat was triturated with ether (2×2 mL)

Sources & evidence

ORD record
ord-75d377c57f2d4be1b1010d0cfe52852c
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

Loading…