Lithium Hydroxide → HCID 23598706, compound

HRID 891209Notes

Reaction equation

HRID 891209 reaction equation
CO[C:3](=[O:37])[CH2:4][N:5]1[CH2:11][C:10]([CH2:12][NH:13][S:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)(=[O:16])=[O:15])=[CH:9][CH2:8][CH:7]([NH:23][C:24]([C:26]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH:29]=[CH:28][N:27]=2)=[O:25])[C:6]1=[O:36].[Li+].[OH-].C(OC(=O)[NH:45][C:46]1[CH:47]([O:52][CH2:53][CH3:54])[O:48][C:49](=[O:51])[CH:50]=1)C=C.C1(S(NCC2CN(CC(O)=O)C(=O)C(NC(C3C4C(=CC=CC=4)C=CN=3)=O)CC=2)(=O)=O)C=CC=CC=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>C1COCC1.O.C(Cl)Cl.C(Cl)Cl.CN(C=O)C.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>[C:17]1([S:14]([NH:13][CH2:12][C:10]2[CH2:11][N:5]([CH2:4][C:3](=[O:37])[NH:45][CH:46]3[CH2:50][C:49](=[O:51])[O:48][CH:47]3[O:52][CH2:53][CH3:54])[C:6](=[O:36])[CH:7]([NH:23][C:24]([C:26]3[C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[CH:29]=[CH:28][N:27]=3)=[O:25])[CH2:8][CH:9]=2)(=[O:16])=[O:15])[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

12

Reactant 6

HCID 3939Lithium HydroxideHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22243188HCID 22243188, compoundHCID 23598692HCID 23598692, compoundHCID 69601293HCID 69601293, compound

Product 1

HCID 23598706HCID 23598706, compound

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 21881883Oxolane--water (1/1)SolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

A solution containing {6-(Benzenesulfonylamino-methyl)-3-[(isoquinoline-1-carbonyl)-amino]-2-oxo-2,3,4,7-tetrahydro-azepin-1-yl}-acetic acid methyl ester (34) (84 mg, 0.17 mmol) in 4 mL of 3:1 THF/H2O was treated with excess LiOH and stirred for 2.5 h at rt. The solution was acidified and extracted with EtOAc. The EtOAc layer was dried (Na2SO4) and concentrated to give the crude carboxylic acid. A catalytic amount of Pd(Ph3P)4 is added to a solution of (2-ethoxy-5-oxo-furan-3-yl)-carbamic acid allyl ester (0.24 g, 1.0 mmol) and N,N-dimethylbarbituric acid (0.38 g, 2.4 mmol) in CH2Cl2 (5 mL). The solution is stirred for 15 minutes at room temperature after which {6-(Benzenesulfonylamino-methyl)-3-[(isoquinoline-1-carbonyl)-amino]-2-oxo-2,3,4,7-tetrahydro-azepin-1-yl}-acetic acid (0.069 g) is added as a solution in CH2Cl2/DMF (2 mL, 1:1), followed by HOBt (0.126 g, 0.93 mmol) and EDCl (0.18 g, 0.93 mmol). The solution is stirred for 5 hours, diluted with EtOAc, washed with saturated NaHCO3 and brine, dried (Na2SO4), and concentrated in vacuo. The resulting residue us purified over silica (EtOAc/hexane) to afford the desired compound.

Workup

  1. extractionextracted with EtOAc
  2. dry with materialThe EtOAc layer was dried (Na2SO4)
  3. concentrationconcentrated
  4. customto give the crude carboxylic acid
  5. stirringThe solution is stirred for 5 hours
  6. washwashed with saturated NaHCO3 and brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customThe resulting residue us purified over silica (EtOAc/hexane)

Sources & evidence

ORD record
ord-d64ca98798ee49798441127730b0f677
Source dataset
uspto-grants-2006_02
Patent number
US07001899B2

Reaction notes

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