4-Methylmorpholine → HCID 23511717, compound

HRID 1968427Notes

Reaction equation

HRID 1968427 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH:16]2[CH:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[CH2:10][CH:9]1C(O)=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CN1CCOCC1.C1(NC(=O)C(O)C(N)CCC)CC1>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH:16]2[CH:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 79724-Methylmorpholine2×HCID 2724699PyBOPHCID 47125101-(tert-Butoxycarbonyl)octahydro-1H-indole-2-carboxylic acidHCID 208049823-Amino-N-cyclopropyl-2-hydroxyhexanamide

Product 1

HCID 23511717HCID 23511717, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Octahydro-indole-1,2-dicarboxylic acid 1-tert-butyl ester 89 (Bachem, 1.6 g, 1.0 eq) in DMF (20 mL) was treated with PyBOP (3.41 g, 1.1 eq) and NMM (1.97 mL, 3.0 eq). To this was added 3-amino-2-hydroxy-hexanoic acid cyclopropylamide 90 (1.22 g, 1.1 eq, prepared according to the procedure of U. Schoellkogf et al., Justus Liebigs Ann. Chem. GE, pp. 183-202 (1976) and J. Semple et al., Org. Letters, 2, pp. 2769-2772 (2000) and NMM (1.97 mL, 3.0 eq) in DMF (3 mL) and the mixture stirred at rt overnight. The mixture was evaporated in vacuo, diluted with ethyl acetate, the organic phase washed with 0.5N HCl, sodium bicarbonate and brine, then dried over sodium sulfate, filtered and concentrated in vacuo to give 2-[1-cyclopropylcarbamoyl-hydroxy-methyl)-butylcarbamoyl]-octahydro-indole-1-carboxylic acid tert-butyl ester 91 which was used without further purification. 1H NMR (CDCl3) δ 6.92 (bs, 1H), 6.80 (bs, 1H), 3.80-4.20 (m, 3H), 2.75 (m, 1H), 2.25 (m, 1H), 2.10 (m, 1H), 1.90-2.00 (m, 2H), 1.5-1.75 (m, 7H), 1.45 (s, 9H), 1.10-1.40 (m, 5H), 0.90 (m, 3H), 0.75 (m, 2H), 0.50 (m, 2H) ppm.

Workup

  1. customprepared
  2. customThe mixture was evaporated in vacuo
  3. additiondiluted with ethyl acetate
  4. washthe organic phase washed with 0.5N HCl, sodium bicarbonate and brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ba51ed510c744e09b47609790bab4323
Source dataset
uspto-grants-2013_04
Patent number
US08426359B2

Reaction notes

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