Diisopropylethylamine → [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 2,2-dimethyl-propyl ester

HRID 346943Notes

Reaction equation

HRID 346943 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][CH2:58][C:59]([CH3:62])([CH3:61])[CH3:60])=[O:56]>C(Cl)Cl.CCOC(C)=O.CO>[CH3:60][C:59]([CH3:62])([CH3:61])[CH2:58][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 3

HCID 81531DiisopropylethylamineHCID 33521852,2-Dimethylpropyl carbonochloridateHCID 86597622HCID 86597622, compound

Product 1

HCID 72427451[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 2,2-dimethyl-propyl esterYield 79%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 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 15 mg (0.1 mmol) of neopentyl 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. The resulting oil was dissolved in methanol and purified by preparative HPLC (YMC XTERRA, S5, 30×50 mm, gradient: 65% B to 100% B, 15 min, hold 2 min, flow rate 40 mL/min) to isolate the product as a white powder (42 mg, 79%): LC-MS (Method A, retention time: 3.58 min), MS m/z 710 (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
  5. custompurified by preparative HPLC (YMC XTERRA, S5, 30×50 mm, gradient: 65% B to 100% B, 15 min, hold 2 min, flow rate 40 mL/min)

Sources & evidence

ORD record
ord-6f2697cfb4c843d49829c42a06c856ae
Source dataset
uspto-grants-2007_02
Patent number
US07173004B2

Reaction notes

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