Dichloromethane → HCID 69601367, compound

HRID 891193Notes

Reaction equation

HRID 891193 reaction equation
[CH2:1]([O:3][C:4](=[O:16])[CH2:5][N:6]1[CH2:12][C:11]([CH3:13])=[CH:10][CH2:9][CH:8]([NH2:14])[C:7]1=[O:15])[CH3:2].C(Cl)Cl.[C:20]1([C:30](O)=[O:31])[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:23]=[CH:22][N:21]=1.ON1C2C=CC=CC=2N=N1>CN(C=O)C.CCOC(C)=O>[CH2:1]([O:3][C:4](=[O:16])[CH2:5][N:6]1[CH2:12][C:11]([CH3:13])=[CH:10][CH2:9][CH:8]([NH:14][C:30]([C:20]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[CH:23]=[CH:22][N:21]=2)=[O:31])[C:7]1=[O:15])[CH3:2]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 68092Isoquinoline-1-carboxylic acidHCID 757711-HydroxybenzotriazoleHCID 131725288HCID 131725288, compound

Product 1

HCID 69601367HCID 69601367, compoundYield 30%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

The crude (3-amino-6-methyl-2-oxo-2,3,4,7-tetrahydroazepin-1-yl}-acetic acid ethyl ester, 10, obtained in the previous step is dissolved in 6 mL of 1:1 DMF:CH2Cl2 and treated with 1-isoquinolinecarboxylic acid (0.24 g, 1.2 mmol), 1-hydroxybenzotriazole (0.23 g, 1.5 mmol), and 1-(3-dimethyl-aminopropyl)-3-ethyl-carbodiimide hydrochloride (0.32 g, 1.5 mmol). The solution is stirred for 1 hour at room temperature, diluted with EtOAc, washed with saturated NaHCO3, saturated NaCl, and dried (Na2SO4). The solvent is removed in vacuo and the crude isolate is purified by HPLC to afford 70 mg (30% yield) of the desired product. 1H NMR (CDCl3) δ 9.51–9.48 (d, J=8.1 Hz, 1H), 9.22–9.20 (d, J=6.9 Hz, 1H), 8.51–8.49 (d, J=5.4 Hz, 1H), 7.84–7.77 (m, 2H), 7.72–7.63 (m, 2H), 5.57 (bs, 1H), 5.48–5.40 (m, 1H), 4.775–4.715 (d, J=18 Hz, 1H), 4.24–4.19 (q, d, J=15.3, 7.5 Hz, 3H), 3.27–3.21 (d, J=18 Hz, 1H), 2.86–2.81 (d, J=16.5 Hz, 1H), 2.45–2.36 (d, d, J=15, 12.6 Hz, 1H), 1.79 (s, 3H), 1.30–1.25 (t, J=7.5 Hz, 3H); 13C (CDCl3) 172.8, 169.2, 165.6, 148.2, 140.8, 137.5, 131.8, 130.5, 128.7, 127.7, 127.0, 124.5, 123.4, 61.6, 52.3, 50.8, 49.6, 32.6, 25.0, 14.3; MS 382 (M+H)+.

Workup

  1. washwashed with saturated NaHCO3, saturated NaCl
  2. dry with materialdried (Na2SO4)
  3. customThe solvent is removed in vacuo
  4. customthe crude isolate
  5. customis purified by HPLC

Sources & evidence

ORD record
ord-93e7deb213294421aa68a290486c0e25
Source dataset
uspto-grants-2006_02
Patent number
US07001899B2

Reaction notes

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