Dichloromethane → N-(Tetrahydro-2H-pyran-2-yloxy) 2-{6-[(naphthalene-2-sulfonyl)-(2-pyrrolidin-1-ylethyl)amino]-3-azabicyclo[3.1.0]hex-3-yl}pyrimidine-5-carboxamide

HRID 2079786Notes

Reaction equation

HRID 2079786 reaction equation
[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][NH:10][C:11]([C:13]1[CH:14]=[N:15][C:16]([N:19]2[CH2:24][CH:23]3[CH:21]([CH:22]3[NH:25][S:26]([C:29]3[CH:38]=[CH:37][C:36]4[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=4)[CH:30]=3)(=[O:28])=[O:27])[CH2:20]2)=[N:17][CH:18]=1)=[O:12].Cl.Cl[CH2:41][CH2:42][N:43]1[CH2:47][CH2:46][CH2:45][CH2:44]1.C(Cl)Cl>CCCCCCC.CN(C=O)C>[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][NH:10][C:11]([C:13]1[CH:14]=[N:15][C:16]([N:19]2[CH2:20][CH:21]3[CH:23]([CH:22]3[N:25]([S:26]([C:29]3[CH:38]=[CH:37][C:36]4[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=4)[CH:30]=3)(=[O:27])=[O:28])[CH2:41][CH2:42][N:43]3[CH2:47][CH2:46][CH2:45][CH2:44]3)[CH2:24]2)=[N:17][CH:18]=1)=[O:12]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 24758Sodium hydride2×HCID 816681-(2-Chloroethyl)pyrrolidine hydrochlorideHCID 59367684N-(Tetrahydro-2H-pyran-2-yloxy) 2-[6-(naphthalene-2-sulfonylamino)-3-azabicyclo[3.1.0]hex-3-yl]pyrimidine-5-carboxamide2×

Product 1

HCID 59367676N-(Tetrahydro-2H-pyran-2-yloxy) 2-{6-[(naphthalene-2-sulfonyl)-(2-pyrrolidin-1-ylethyl)amino]-3-azabicyclo[3.1.0]hex-3-yl}pyrimidine-5-carboxamideYield 19.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8900HeptaneSolvent

Procedure

NaH (0.223 g, 5.5 mmol) was washed with heptane (10 ml), then suspended in DMF (5 ml). N-(Tetrahydro-2H-pyran-2-yloxy) 2-{6-[(naphthalene-2-sulfonyl)amino]-3-azabicyclo[3.1.0]hex-3-yl}pyrimidine-5-carboxamide (0.991 g, 1.95 mmol) was added, and the mixture stirred for 5 min. To NaH (0.172 g, 4.3 mmol) in DMF was added 1-(2-chloroethyl)-pyrrolidine hydrochloride (0.724 g, 4.2 mmol). The reaction was swirled gently for 2 min, and then added to the solution of N-(tetrahydro-2H-pyran-2-yloxy) 2-{6-[(naphthalene-2-sulfonyl)amino]-3-azabicyclo[3.1.0]hex-3-yl}pyrimidine-5-carboxamide. The mixture was stirred at r.t. for 5 days, then poured into DCM (150 ml) and quenched with 2.4M ammonium chloride solution (50 ml). The organic layer was separated, and the aqueous was further extracted with DCM (150 ml). The combined organic extracts were dried, concentrated in vacuo to give the title compound (0.234 g, 19%). This was carried forward without further purification.

Workup

  1. waitThe reaction was swirled gently for 2 min
  2. stirringThe mixture was stirred at r.t. for 5 days
  3. customquenched with 2.4M ammonium chloride solution (50 ml)
  4. customThe organic layer was separated
  5. extractionthe aqueous was further extracted with DCM (150 ml)
  6. customThe combined organic extracts were dried
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-75ec557e165645dd98d93dc90fcc1e5b
Source dataset
uspto-grants-2011_04
Patent number
US07932246B2

Reaction notes

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