Diisopropylethylamine → 2-[(Isoquinoline-4-carbonyl)-amino]-indan-2-carboxylic acid ethyl ester

HRID 1047707Notes

Reaction equation

HRID 1047707 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([C:11]([OH:13])=O)=[CH:3][N:2]=1.[CH2:14]([O:16][C:17]([C:19]1([NH2:28])[CH2:27][C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:20]1)=[O:18])[CH3:15].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH2:14]([O:16][C:17]([C:19]1([NH:28][C:11]([C:4]2[C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH:1]=[N:2][CH:3]=2)=[O:13])[CH2:27][C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:20]1)=[O:18])[CH3:15]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 459768Isoquinoline-4-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10921653Ethyl 2-amino-2,3-dihydro-1H-indene-2-carboxylate

Product 1

HCID 593141882-[(Isoquinoline-4-carbonyl)-amino]-indan-2-carboxylic acid ethyl esterYield 82%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of isoquinoline-4-carboxylic acid (211 mg, 1.22 mmol), 2-amino-indan-2-carboxylic acid ethyl ester (250 mg, 1.22 mmol), HATU (696 mg, 1.83 mmol) in anhydrous DMF (8 mL) is added DIPEA (302 μL, 1.83 mmol). The resulting solution is stirred at RT overnight. After the removal of DMF in vacuo, the residue is dissolved in EtOAc (40 mL) and washed with water (1×10 mL) and brine (2×10 mL). The organic layer is dried over anhydrous Na2SO4 and concentrated in vacuo. The residue is purified by flash column chromatography (115 g silica gel, gradient elution: 5-50% EtOAc in heptane) to give a pure product (51) as white solid (359 mg, 82%).

Workup

  1. customAfter the removal of DMF in vacuo
  2. dissolutionthe residue is dissolved in EtOAc (40 mL)
  3. washwashed with water (1×10 mL) and brine (2×10 mL)
  4. dry with materialThe organic layer is dried over anhydrous Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by flash column chromatography (115 g silica gel, gradient elution: 5-50% EtOAc in heptane)

Sources & evidence

ORD record
ord-a62c408258c0485d86f193d7913cdc9e
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

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