PyBOP → 14-(1-(Bis(tert-butoxycarbonyl)amino)isoquinolin-6-ylamino)-2-oxa-5,12-diaza-tricyclo[13.2.2.16,10]icosa-1(18),6(20),7,9,15(19),16-hexaene-4,13-dione

HRID 735676Notes

Reaction equation

HRID 735676 reaction equation
C([O:8][C:9]([NH:11][CH2:12][C:13]1[CH:14]=[C:15]([NH:19][C:20](=[O:59])[CH2:21][O:22][C:23]2[CH:28]=[CH:27][C:26]([CH:29]([NH:33][C:34]3[CH:35]=[C:36]4[C:41](=[CH:42][CH:43]=3)[C:40]([N:44]([C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])[C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])=[N:39][CH:38]=[CH:37]4)C(O)=O)=[CH:25][CH:24]=2)[CH:16]=[CH:17][CH:18]=1)=O)C1C=CC=CC=1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C.CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:48]([O:47][C:45]([N:44]([C:52]([O:54][C:55]([CH3:57])([CH3:56])[CH3:58])=[O:53])[C:40]1[C:41]2[C:36](=[CH:35][C:34]([NH:33][CH:29]3[C:26]4=[CH:27][CH:28]=[C:23]([CH:24]=[CH:25]4)[O:22][CH2:21][C:20](=[O:59])[NH:19][C:15]4=[CH:14][C:13](=[CH:18][CH:17]=[CH:16]4)[CH2:12][NH:11][C:9]3=[O:8])=[CH:43][CH:42]=2)[CH:37]=[CH:38][N:39]=1)=[O:46])([CH3:49])([CH3:51])[CH3:50]

Participants

6

Reactant 2

HCID 2724699PyBOPHCID 578426372-(4-(2-(3-((Benzyloxycarbonylamino)methyl)phenylamino)-2-oxoethoxy)phenyl)-2-(1-(bis(tert-butoxycarbonyl)amino)isoquinolin-6-ylamino)acetic acid

Product 1

HCID 5784289714-(1-(Bis(tert-butoxycarbonyl)amino)isoquinolin-6-ylamino)-2-oxa-5,12-diaza-tricyclo[13.2.2.16,10]icosa-1(18),6(20),7,9,15(19),16-hexaene-4,13-dioneYield 16%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 66D (55 mg, 0.082 mmol) in 10 mL DMF was added to a solution of PyBOP (88 mg, 0.17 mmol), DMAP (49 mg, 0.4 mmol), and TEA (40 mg, 0.4 mmol) in CH2Cl2 (30 mL) dropwise through syringe pump over 3 h. The solution was stirred at rt for 16 h. The solution washed with 1M H3PO4, sat NaHCO3 and brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (0 to 80% EtOAc in hexanes) to give 66F (8.5 mg, 16%). MS (ESI) m/z 654.8 (M+H)+.

Workup

  1. washThe solution washed with 1M H3PO4
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated
  4. customThe crude product was purified by flash chromatography (0 to 80% EtOAc in hexanes)

Sources & evidence

ORD record
ord-0517fa9b27cf461e9a54cee34a23d65c
Source dataset
uspto-grants-2009_09
Patent number
US07592331B2

Reaction notes

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