1-Hydroxybenzotriazole → isoquinoline-1-carboxylic acid {1-[(2-ethoxy-5-oxo-tetra-hydrofuran-3-ylcarbamoyl)methyl]-2-oxo-2,3,4,7-tetrahydro-1H-azepin-3-yl} amide

HRID 891191Notes

Reaction equation

HRID 891191 reaction equation
C(O[C:5](=[O:16])[NH:6][CH:7]1[CH2:11][C:10](=[O:12])[O:9][CH:8]1[O:13][CH2:14][CH3:15])C=C.[C:17]1([C:27]([NH:29][CH:30]2[CH2:36][CH:35]=[CH:34][CH2:33][N:32]([CH2:37]C(O)=O)[C:31]2=[O:41])=[O:28])[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:20]=[CH:19][N:18]=1.ON1C2C=CC=CC=2N=N1>C(Cl)Cl.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:14]([O:13][CH:8]1[CH:7]([NH:6][C:5]([CH2:37][N:32]2[CH2:33][CH:34]=[CH:35][CH2:36][CH:30]([NH:29][C:27]([C:17]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[CH:20]=[CH:19][N:18]=3)=[O:28])[C:31]2=[O:41])=[O:16])[CH2:11][C:10](=[O:12])[O:9]1)[CH3:15]

Participants

7

Reactant 3

HCID 757711-HydroxybenzotriazoleHCID 22149038(2-Ethoxy-5-oxo-tetrahydrofuran-3-yl)-carbamic acid allyl esterHCID 23598657{3-[(Isoquinolin-1-carbonyl)amino]-2-oxo-2,3,4,7-tetrahydro-azepin-1-yl} acetic acid

Product 1

HCID 86590750isoquinoline-1-carboxylic acid {1-[(2-ethoxy-5-oxo-tetra-hydrofuran-3-ylcarbamoyl)methyl]-2-oxo-2,3,4,7-tetrahydro-1H-azepin-3-yl} amide

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A catalytic amount of Pd(Ph3P)4 is added to a solution of (2-ethoxy-5-oxo-tetrahydrofuran-3-yl)-carbamic acid allyl ester (338 mg, 1.48 mmol) and N,N-dimethylbarbituric acid (483 mg, 3.1 mmol) in CH2Cl2 (5 mL) at room temperature. The solution is stirred for 15 min then {3-[(isoquinolin-1-carbonyl)amino]-2-oxo-2,3,4,7-tetrahydro-azepin-1-yl} acetic acid, 5, (178 mg) as prepared above is added as a solution in CH2Cl2 (1 mL) followed by 1-hydroxybenzotriazole (416 mg, 3.1 mmol) and 1-(3-dimethyl-aminopropyl)-3-ethyl-carbodiimide hydrochloride (584 mg, 3.1 mmol). The solution is stirred for an additional 3 hours, then diluted with EtOAc, washed with saturated NaHCO3, brine, dried (MgSO4), and concentrated in vacuo to afford the desired product in sufficient purity to be used directly.

Workup

  1. stirringThe solution is stirred for an additional 3 hours
  2. washwashed with saturated NaHCO3, brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c7275a9b957d4187b1e0eeb7a11253ec
Source dataset
uspto-grants-2006_02
Patent number
US07001899B2

Reaction notes

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