Oxane-4-carboxylic acid → HCID 10320019, compound

HRID 645868Notes

Reaction equation

HRID 645868 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([C:7]([OH:9])=O)[CH2:3][CH2:2]1.O.ON1C2C=CC=CC=2N=N1.[CH:21]1([N:25]2[CH2:31][CH2:30][C:29]3[CH:32]=[CH:33][C:34]([O:36][C:37]4[N:42]=[CH:41][C:40]([NH2:43])=[CH:39][CH:38]=4)=[CH:35][C:28]=3[CH2:27][CH2:26]2)[CH2:24][CH2:23][CH2:22]1>ClCCl>[CH:21]1([N:25]2[CH2:26][CH2:27][C:28]3[CH:35]=[C:34]([O:36][C:37]4[N:42]=[CH:41][C:40]([NH:43][C:7]([CH:4]5[CH2:3][CH2:2][O:1][CH2:6][CH2:5]5)=[O:9])=[CH:39][CH:38]=4)[CH:33]=[CH:32][C:29]=3[CH2:30][CH2:31]2)[CH2:22][CH2:23][CH2:24]1

Participants

5

Reactant 3

HCID 219302Oxane-4-carboxylic acidHCID 27960291-Hydroxybenzotriazole hydrateHCID 10244844HCID 10244844, compound

Product 1

HCID 10320019HCID 10320019, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Tetrahydro-pyran-4-carboxylic acid (252 mg, 1.94 mmol), 1-hydroxy benzotriazole hydrate (262 mg, 1.94 mmol) and N-cyclohexylcarbodiimide N′-methyl polystyrene (1.7 mmol/g, 2.3 g, 3.88 mmol) were stirred at room temperature in dichloromethane (10 ml) for 15 minutes. 6-[(3-Cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-3-pyridinamine (E236) (300 mg, 0.97 mmol) was added and stirring continued for 16 hours. The reaction mixture was applied to a SCX ion exchange cartridge (Varian bond-elute, 5 g) and washed with methanol and then a mixture of 0.880 ammonia/methanol. The combined basic fractions were concentrated in vacuo and the resulting residue was purified by column chromatography eluting with a mixture of 0.880 ammonia:methanol:dichloromethane (0.5:4.5:95) to afford the title product (E241); MS (ES+) m/e 422 [M+H]+.

Workup

  1. washwashed with methanol
  2. additiona mixture of 0.880 ammonia/methanol
  3. concentrationThe combined basic fractions were concentrated in vacuo
  4. customthe resulting residue was purified by column chromatography
  5. washeluting with a mixture of 0.880 ammonia:methanol:dichloromethane (0.5:4.5:95)

Sources & evidence

ORD record
ord-f289ab65a2bd447897afea9261eef450
Source dataset
uspto-grants-2010_04
Patent number
US07704994B2

Reaction notes

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