Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → HCID 131729548, compound

HRID 1687025Notes

Reaction equation

HRID 1687025 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:21]=[CH:20][C:12]3[CH2:13][CH2:14][N:15]([CH2:18][CH3:19])[CH2:16][CH2:17][C:11]=3[CH:10]=2)[C:5]([Cl:22])=[CH:4][N:3]=1.[CH2:23]([N:25]1[CH2:31][CH2:30][C:29]2[CH:32]=[C:33](N)[CH:34]=[CH:35][C:28]=2[CH2:27][CH2:26]1)[CH3:24].[C:37]12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>C(O)(C)C>[Cl:22][C:5]1[C:6]([NH:8][C:9]2[CH:21]=[CH:20][C:12]3[CH2:13][CH2:14][N:15]([CH2:18][CH3:19])[CH2:16][CH2:17][C:11]=3[CH:10]=2)=[CH:37][C:2]([NH:7][C:33]2[CH:34]=[CH:35][C:28]3[CH2:27][CH2:26][N:25]([CH2:23][CH3:24])[CH2:31][CH2:30][C:29]=3[CH:32]=2)=[N:3][CH:4]=1

Participants

5

Reactant 3

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-2×HCID 189434013-Ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamineHCID 86633863HCID 86633863, compound

Product 1

HCID 131729548HCID 131729548, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

(2,5-dichloro-pyrimidin-4-yl)-(3-ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl)-amine (50 mg, 0.15 mmol) and 3-ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine (29 mg, 0.15 mmol) were combined with camphorsulfonic acid (74 mg, 0.32 mmol) in 5 mL isopropyl alcohol and subjected to microwave irradiation at 120° C. for 80 minutes. 35 mg addition camphorsulfonic acid was added and microwave irradiation was continued for an additional hour. The mixture was concentrated and the organics were partitioned between dichloromethane and saturated sodium bicarbonate solution. The organic layer was separated, was dried (sodium sulfate), and was concentrated. The solid was obtained was triturated with ether. The ether was separated and concentrated and the solid obtained was purified by reverse phase chromatography (0% to 30% acetonitrile:water on C8) to afford 55 mg (76%) of 5-Chloro-N*2*,N*4*-bis-(3-ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl)-pyridine-2,4-diamine as a white solid. Mp: 132-4° C.; MS: 493.41 (M+2H); 1H NMR (chloroform-d): δ 8.04 (s, 1H), δ 7.41 (d, J=8 Hz, 1H), δ 7.28 (m, 2H), δ 7.09 (d, J=8 Hz, 1H), δ 7.02 (m, 2H), δ 6.90 (br s, 1H), δ 3.00-2.85 (m, 8H), δ 2.76-2.54 (m, 12H), δ 1.17 (m, 6H).

Workup

  1. customirradiation at 120° C. for 80 minutes
  2. additionwas added
  3. custommicrowave irradiation
  4. waitwas continued for an additional hour
  5. concentrationThe mixture was concentrated
  6. customthe organics were partitioned between dichloromethane and saturated sodium bicarbonate solution
  7. customThe organic layer was separated
  8. dry with materialwas dried (sodium sulfate)
  9. concentrationwas concentrated
  10. customThe solid was obtained
  11. customwas triturated with ether
  12. customThe ether was separated
  13. concentrationconcentrated
  14. customthe solid obtained
  15. customwas purified by reverse phase chromatography (0% to 30% acetonitrile:water on C8)

Sources & evidence

ORD record
ord-11608b90086c46018c47053f2c7aee8f
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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