Tetrahydrofuran → n-(1-Isobutoxyethoxy) 2-[6-(naphthalene-2-sulfonylamino)-3-azabicyclo[3.1.0]hex-3-yl]pyrimidine-5-carboxamide

HRID 2079783Notes

Reaction equation

HRID 2079783 reaction equation
CCN=C=N[CH2:6][CH2:7][CH2:8]N(C)C.Cl.[CH:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[CH:15][C:14]=1[S:23]([NH:26][CH:27]1[CH:32]2[CH:28]1[CH2:29][N:30]([C:33]1[N:38]=[CH:37][C:36]([C:39]([OH:41])=O)=[CH:35][N:34]=1)[CH2:31]2)(=[O:25])=[O:24].CCN(CC)CC.C1C=CC2[N:57]([OH:58])N=NC=2C=1.C1[CH2:63][O:62][CH2:61][CH2:60]1>C(Cl)Cl>[CH2:63]([O:62][CH:61]([O:58][NH:57][C:39]([C:36]1[CH:35]=[N:34][C:33]([N:30]2[CH2:29][CH:28]3[CH:32]([CH:27]3[NH:26][S:23]([C:14]3[CH:15]=[CH:16][C:17]4[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=4)[CH:13]=3)(=[O:25])=[O:24])[CH2:31]2)=[N:38][CH:37]=1)=[O:41])[CH3:60])[CH:7]([CH3:6])[CH3:8]

Participants

7

Reactant 5

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 59367693HCID 59367693, compound

Product 1

HCID 59367652n-(1-Isobutoxyethoxy) 2-[6-(naphthalene-2-sulfonylamino)-3-azabicyclo[3.1.0]hex-3-yl]pyrimidine-5-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

EDCl (7.27 g, 37.9 mmol) was added to a suspension of 2-{6-[(2-napthylsulphonyl)amino]-3-azabicyclo[3.1.0]hex-3-yl}pyrimidine-5-carboxylic acid (22.19 g, 54.12 mmol) in anhydrous DCM (100 ml) and anhydrous THF (500 ml) at r.t. under N2. Et3N (22.6 ml, 162.14 mmol) was added followed by HOBt (8.78 g, 64.97 mmol) and intermediate D (8.9 ml, 64.89 mmol). After stirring at r.t. for 6 days LCMS indicated 78% conversion to the required product. The reaction mixture was retreated with EDCl (10.25 g, 53.47 mmol), HOBt (7.22 g, 53.43 mmol) and Et3N (19.4 ml, 139.00 mmol). After stirring for another 3 days at r.t. LCMS showed 96% conversion. The reaction mixture was evaporated to dryness and suspended in EtOAc (100 ml) and water (100 ml). A white solid was collected by filtration, washed with EtOAc (50 ml), water (50 ml), MeOH (50 ml) and dried in vacuo to give the crude product as a white solid (30 g, LCMS purity 92%). This was stirred in EtOH (1500 ml) at 60° C. for 1 h giving a white suspension which was cooled to r.t., filtered and air dried to give the title compound as a white solid (24.0 g, 87%). LCMS purity 97%, m/z 511 [M+H]+, 1H NMR (400 MHz, d6-DMSO) δ: 1.60-1.75 (6H, m), 1.80 (2H, s), 1.90 (1H, s), 4.50 (3H, m), 4.65 (2H, d), 4.00 (1H, m), 4.95 (1H, t), 7.60 (2H, m), 7.80-8.30 (4H, d), 8.50 (1H, s), 8.65 (2H, s).

Sources & evidence

ORD record
ord-147edf911b58474fa54278d244a4b57e
Source dataset
uspto-grants-2011_04
Patent number
US07932246B2

Reaction notes

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