Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → 2-[5-Bromo-2-(3-dimethylcarbamoylmethyl-8-methoxy-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide

HRID 1040862Notes

Reaction equation

HRID 1040862 reaction equation
[Br:1][C:2]1[C:3]([NH:9][C:10]2[CH:19]=[CH:18][CH:17]=[CH:16][C:11]=2[C:12]([NH:14][CH3:15])=[O:13])=[N:4][C:5](Cl)=[N:6][CH:7]=1.[NH2:20][C:21]1[C:37]([O:38][CH3:39])=[CH:36][C:24]2[CH2:25][CH2:26][N:27]([CH2:30][C:31]([N:33]([CH3:35])[CH3:34])=[O:32])[CH2:28][CH2:29][C:23]=2[CH:22]=1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>C(O)(C)C>[Br:1][C:2]1[C:3]([NH:9][C:10]2[CH:19]=[CH:18][CH:17]=[CH:16][C:11]=2[C:12]([NH:14][CH3:15])=[O:13])=[N:4][C:5]([NH:20][C:21]2[C:37]([O:38][CH3:39])=[CH:36][C:24]3[CH2:25][CH2:26][N:27]([CH2:30][C:31](=[O:32])[N:33]([CH3:34])[CH3:35])[CH2:28][CH2:29][C:23]=3[CH:22]=2)=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 587484682-(5-Bromo-2-chloro-pyrimidin-4-ylamino)-N-methyl-benzamideHCID 672635242-(7-amino-8-methoxy-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-N,N-dimethylacetamide

Product 1

HCID 668302282-[5-Bromo-2-(3-dimethylcarbamoylmethyl-8-methoxy-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamideYield 51%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
120 °C

Procedure

2-(5-Bromo-2-chloro-pyrimidin-4-ylamino)-N-methyl-benzamide (50 mg, 0.161 mmol), 2-(7-amino-8-methoxy-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-N,N-dimethyl-acetamide (44 mg, 0.161 mmol) and camphorsulfonic acid (56 mg, 0.241 mmol) were combined in 3 mL isopropanol and heated at 120° C. in microwave for a total of 90 min. The reaction was concentrated to be taken up in dichloromethane and washed with saturated sodium bicarbonate solution (2×30 mL). The organic layer was dried over MgSO4 and filtered. The filtrate was chromatographed on a 4 g amine capped ISCO flash column from 0-100% ethyl acetate in hexanes. The product was collected as a foam after concentrating to afford 43 mg (51%) of a yellow foam. Compound 6: mp 225° C.; MS (ES+ calculated” 582; found: 583 M+H). 1H NMR (400 MHz, CDCl3) δ 10.81 (s, 1H), 8.59 (d, J=8, 1H), 8.21 (s, 1H), 8.07 (s, 1H), 7.49 (m, 3H), 7.10 (t, J=7 Hz, 1H), 6.65 (s, 1H), 6.29 (s, 1H), 3.88 (s, 3H), 3.29 (s, 2H), 3.16 (s, 3H), 3.05 (d, J=4, 3H), 2.99 (s, 3H), 2.89 (s, 2H), 2.77 (s, 2H), 2.71 (s, 6H), 1.66 (br s, 1H) ppm.

Workup

  1. concentrationThe reaction was concentrated
  2. washwashed with saturated sodium bicarbonate solution (2×30 mL)
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. customThe filtrate was chromatographed on a 4 g amine capped ISCO flash column from 0-100% ethyl acetate in hexanes
  6. customThe product was collected as a foam
  7. concentrationafter concentrating

Sources & evidence

ORD record
ord-3da8f8757665436d9ab012084253997e
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

Loading…