Diisopropylethylamine → HCID 59410798, compound

HRID 2209353Notes

Reaction equation

HRID 2209353 reaction equation
[C:1]([N:8]1[C@@H:17](C(O)=O)[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C[C@@H](O)[C@@H]1NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC2C=CC=CC=2)NC(=O)[C@H](CCN)NC(=O)[C@@H](NC([C@@H](N)CCN)=O)CCN[C:24]1=[O:25].OS(O)(=O)=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.[CH3:120][C:121]([CH3:141])=[CH:122][CH2:123][CH2:124]/[C:125](/[CH3:140])=[CH:126]/[CH2:127][CH2:128]/[C:129](/[CH3:139])=[CH:130]/[CH2:131][S:132][CH2:133][C@H:134]([NH2:138])[C:135]([OH:137])=[O:136]>C(Cl)Cl>[C:4]([O:3][C:1]([N:8]1[C@@H:17]([C:24]([NH:138][C@@H:134]([CH2:133][S:132][CH2:131]/[CH:130]=[C:129](\[CH3:139])/[CH2:128][CH2:127]/[CH:126]=[C:125](\[CH3:140])/[CH2:124][CH2:123][CH:122]=[C:121]([CH3:141])[CH3:120])[C:135]([OH:137])=[O:136])=[O:25])[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9]1)=[O:2])([CH3:5])([CH3:7])[CH3:6]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 197465Dab-cyclo(dab-dab-phe-leu-dab-dab-thr) sulfate saltHCID 688607(3R)-2-[(tert-butoxy)carbonyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acidHCID 6438372FarnesylcysteineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 59410798HCID 59410798, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a 100 mL round bottom flask, N-Boc-(R)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (1.0 mmol), coupling reagent (520 mg of PBOP or 380 mg of HATU, 1 mmol) and N,N-diisopropyl-ethyl-amine (650 mg, 5 mmol) were mixed in CH2Cl2 (10 mL). The reaction mixture was stirred at room temperature for 30 minutes. S-trans, trans-farnesyl-L-cysteine (325 mg, 1 mmol) was added to the reaction mixture and stirred at room temperature overnight. CH2Cl2 was removed by rotary evaporation. The resulting residue was dissolved in ethyl acetate (50 mL). The organic solution was washed with an NH4Cl saturated solution (50 mL), dried over Na2SO4, and concentrated to afford a crude mixture. The crude mixture was purified by preparative HPLC (250 mg, 48%) to yield Compound N-50. 1H-NMR (500 MHz, CD3OD): δ 1.33 (s, 9H), 1.61 (bs, 6H), 1.68 (bs, 6H), 1.69-1.73 (m, 2H), 1.99 (t, J=7.5 Hz, 2H), 2.06-2.17 (m, 8H), 2.73 (dd, J=7.5, 14.0, 1H), 2.87 (dd, J=5.0, 14.0 Hz, 1H), 3.16 (dd, J=7.5, 13.0 Hz, 1H), 3.25 (dd, J=8.0, 13.0 Hz, 1H), 3.25-3.30 (m, 2H), 3.73 (dd, J=5.5, 14.0 Hz, 1H), 4.55-4.61 (m, 2H), 5.12 (dd, J=8.0, 17.0 Hz, 2H), 5.20 (t, J=7.5 Hz, 1H), 7.39-7.88 (m, 3H), 8.20-8.24 (m, 1H). 13C-NMR (125 MHz, CD3OD): δ 16.2, 16.3, 17.9, 26.0, 27.4, 27.8, 28.1, 28.7, 30.4, 30.5, 30.9, 33.4, 36.6, 37.9, 40.8, 40.9, 53.3, 56.9, 57.7, 121.5, 124.8, 125.1, 125.5, 126.5, 126.6, 127.3, 128.6, 128.7, 128.8, 129.3, 129.9, 132.1, 133.5, 134.7, 135.5, 136.3, 140.6, 157.5, 173.7, 174.2; ES-MS: mass calcd for Chemical Formula: C33H48N2O5S 584.8. Found (M+Na) m/z 607.4.

Workup

  1. stirringstirred at room temperature overnight
  2. customCH2Cl2 was removed by rotary evaporation
  3. dissolutionThe resulting residue was dissolved in ethyl acetate (50 mL)
  4. washThe organic solution was washed with an NH4Cl saturated solution (50 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customto afford a crude mixture
  8. customThe crude mixture was purified by preparative HPLC (250 mg, 48%)

Sources & evidence

ORD record
ord-a6adf6727e0344a282f9fe54874cb1bb
Source dataset
uspto-grants-2016_06
Patent number
US09376383B2

Reaction notes

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