Diisopropylethylamine → 4,4-Dimethyl-7-{2-[(2-methylamino-pyrimidin-4-ylmethyl)-amino]-benzoylamino}-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

HRID 969696Notes

Reaction equation

HRID 969696 reaction equation
[CH3:1][NH:2][C:3]1[N:8]=[C:7]([CH2:9][NH:10][C:11]2[CH:19]=[CH:18][CH:17]=[CH:16][C:12]=2[C:13]([OH:15])=O)[CH:6]=[CH:5][N:4]=1.[C:20]([O:24][C:25]([N:27]1[CH2:36][C:35]([CH3:38])([CH3:37])[C:34]2[C:29](=[CH:30][C:31]([NH2:39])=[CH:32][CH:33]=2)[CH2:28]1)=[O:26])([CH3:23])([CH3:22])[CH3:21].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[C:20]([O:24][C:25]([N:27]1[CH2:36][C:35]([CH3:38])([CH3:37])[C:34]2[C:29](=[CH:30][C:31]([NH:39][C:13](=[O:15])[C:12]3[CH:16]=[CH:17][CH:18]=[CH:19][C:11]=3[NH:10][CH2:9][C:7]3[CH:6]=[CH:5][N:4]=[C:3]([NH:2][CH3:1])[N:8]=3)=[CH:32][CH:33]=2)[CH2:28]1)=[O:26])([CH3:23])([CH3:21])[CH3:22]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 21959561Tert-butyl 7-amino-4,4-dimethyl-3,4-dihydroisoquinoline-2(1H)-carboxylateHCID 695125122-[(2-Methylamino-pyrimidin-4-ylmethyl)-amino]-benzoic acid

Product 1

HCID 695103884,4-Dimethyl-7-{2-[(2-methylamino-pyrimidin-4-ylmethyl)-amino]-benzoylamino}-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-[(2-methylamino-pyrimidin-4-ylmethyl)-amino]-benzoic acid (Step C, 0.31 g, 1.20 mmol), 7-amino-4,4-dimethyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (0.33 g, 1.20 mmol), TBTU (0.43 g, 1.32 mmol), and DIEA (0.31 mL, 1.80 mmol) in 10 mL of DMF was stirred at RT for 2 h. The mixture was partitioned between EtOAc and Na2CO3 (aq). The organic layer was washed with water, brine, dried with MgSO4, filtered, condensed, and the residue was purified by flash column chromatography (0 to 30% of EtOAc in CH2Cl2). The titled compound was obtained as a light yellowish solid. MS (ES+): 517.4 (M+H)+. Calc'd for C29H36N6O3-516.63

Workup

  1. customThe mixture was partitioned between EtOAc and Na2CO3 (aq)
  2. washThe organic layer was washed with water, brine
  3. dry with materialdried with MgSO4
  4. filtrationfiltered
  5. customcondensed
  6. customthe residue was purified by flash column chromatography (0 to 30% of EtOAc in CH2Cl2)

Sources & evidence

ORD record
ord-9e5ed32444854af3a79fc165cbfe878c
Source dataset
uspto-grants-2007_12
Patent number
US07307088B2

Reaction notes

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