Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → HCID 66830613, compound

HRID 1041638Notes

Reaction equation

HRID 1041638 reaction equation
[C:1]([CH2:3][CH2:4][N:5]([CH3:23])[C:6](=[O:22])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[NH:13][C:14]1[C:19]([Cl:20])=[CH:18][N:17]=[C:16](Cl)[N:15]=1)#[N:2].[NH2:24][C:25]1[CH:26]=[CH:27][C:28]2[N:34]([CH3:35])[C:33](=[O:36])[CH2:32][CH2:31][CH2:30][C:29]=2[CH:37]=1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.C(=O)(O)[O-].[Na+]>C(O)(C)C>[Cl:20][C:19]1[C:14]([NH:13][C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[C:6]([N:5]([CH2:4][CH2:3][C:1]#[N:2])[CH3:23])=[O:22])=[N:15][C:16]([NH:24][C:25]2[CH:26]=[CH:27][C:28]3[N:34]([CH3:35])[C:33](=[O:36])[CH2:32][CH2:31][CH2:30][C:29]=3[CH:37]=2)=[N:17][CH:18]=1

Participants

6

Reactant 4

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 516892Sodium BicarbonateHCID 197602587-Amino-1-methyl-1,3,4,5-tetrahydro-benzo[B]azepin-2-oneHCID 86634063HCID 86634063, compound

Product 1

HCID 66830613HCID 66830613, compoundYield 35%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

N-(2-Cyano-ethyl)-2-(2,5-dichloro-pyrimidin-4-ylamino)-N-methyl-benzamide (101 mg, 0.288 mmol), 7-Amino-1-methyl-1,3,4,5-tetrahydro-1-benzazepin-2-one (48 mg, 0.25 mmol), and 10-Camphorsulfonic acid (5.0 mg, 0.022 mmol) in Isopropyl alcohol (2.0 mL) were added into a microwave vial and irradiated at 120° C. for 30 min. The reaction was diluted with satd. sodium bicarbonate (5 mL) and cooled to aid in precipitate formation. The solids were collected and washed with 7 mL water. The solids contained product with starting chloropyrimidine and another impurity. The filtrate contained the aniline component, product and other impurities. The filtrate was extracted 3×10 mL DCM, dried and concentrated. The solids were chromatographed (ISCO, 12 g silica gel, 0-100% EtOAc:Hex) separately from the filtrate, and clean fractions were combined to give the product as a yellow foam (44 mg, 35%). LCMS: 504 (M+H), 1H-NMR (CDCl3): 8.93 (s, 1H), 8.34 (d, 1H, J=8.2 Hz), 8.10 (s, 1H), 7.44 (m, 3H), 7.37 (d, 1H, J=7.8 Hz), 7.18 (dd, 1H, J=7.4, 7.4 Hz), 7.07 (d, 1H, J=8.3 Hz), 6.95 (s, 1H), 3.81 (br s, 2H), 3.33 (s, 3H), 3.20 (s, 3H), 2.81 (br s, 2H), 2.64 (m, 2H), 2.32 (t, 2H, J=7.2 Hz), 2.15 (m, 2H).

Workup

  1. customirradiated at 120° C. for 30 min
  2. additionThe reaction was diluted with satd
  3. customThe solids were collected
  4. washwashed with 7 mL water
  5. extractionThe filtrate was extracted 3×10 mL DCM
  6. customdried
  7. concentrationconcentrated
  8. customThe solids were chromatographed (ISCO, 12 g silica gel, 0-100% EtOAc:Hex) separately from the filtrate, and clean fractions

Sources & evidence

ORD record
ord-660830a2581b48709b12fc551cf67005
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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