Methyl chloroformate → [4-Cyclopropanesulfonylaminocarbonyl-18-(isoquinolin-1-yloxy)-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-7-en-14-yl]-carbamic acid methyl ester

HRID 346942Notes

Reaction equation

HRID 346942 reaction equation
Cl.Cl.[NH2:3][CH:4]1[C:22](=[O:23])[N:21]2[CH:17]([CH2:18][CH:19]([O:24][C:25]3[C:34]4[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=4)[CH:28]=[CH:27][N:26]=3)[CH2:20]2)[C:16](=[O:35])[NH:15][C:14]2([C:36]([NH:38][S:39]([CH:42]3[CH2:44][CH2:43]3)(=[O:41])=[O:40])=[O:37])[CH:12]([CH2:13]2)[CH:11]=[CH:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]1.CCN(C(C)C)C(C)C.Cl[C:55]([O:57][CH3:58])=[O:56].CO.C(Cl)Cl>C(Cl)Cl.CCOC(C)=O>[CH3:58][O:57][C:55](=[O:56])[NH:3][CH:4]1[C:22](=[O:23])[N:21]2[CH:17]([CH2:18][CH:19]([O:24][C:25]3[C:34]4[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=4)[CH:28]=[CH:27][N:26]=3)[CH2:20]2)[C:16](=[O:35])[NH:15][C:14]2([C:36]([NH:38][S:39]([CH:42]3[CH2:43][CH2:44]3)(=[O:40])=[O:41])=[O:37])[CH:12]([CH2:13]2)[CH:11]=[CH:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]1

Participants

7

Reactant 4

HCID 6586Methyl chloroformateHCID 81531DiisopropylethylamineHCID 21226129Dichloromethane methanolHCID 86597622Cyclopropanesulfonic acid [14-amino-18-(isoquinolin-1-yloxy)-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-7-ene-4-carbonyl)-amide bis hydrochloride

Product 1

HCID 72427492[4-Cyclopropanesulfonylaminocarbonyl-18-(isoquinolin-1-yloxy)-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-7-en-14-yl]-carbamic acid methyl esterYield 82%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of cyclopropanesulfonic acid [14-amino-18-(isoquinolin-1-yloxy)-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-7-ene-4-carbonyl]-amide bis hydrochloride (50 mg, 0.075 mmol) in 2 mL of DCM was added 44 μL (0.25 mmol)of DIPEA and 9 mg (0.10 mmol) of methyl chloroformate. The mixture was stirred at rt for 2 h. It was then diluted with EtOAc and washed with pH 4 buffer (2×) and brine (1×). The organic phase was dried (MgSO4) and concentrated in vacuo to give the crude product. Flash chromatography (2% MeOH/DCM) gave 40 mg (82%) of the desired product as a white solid: LC-MS (Method A, retention time: 3.05 min), MS m/z 654 (M++1).

Workup

  1. washwashed with pH 4 buffer (2×) and brine (1×)
  2. dry with materialThe organic phase was dried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customto give the crude product

Sources & evidence

ORD record
ord-76b605ece3d243c485393b0a6912210a
Source dataset
uspto-grants-2007_02
Patent number
US07173004B2

Reaction notes

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