4-Methylmorpholine → 3-(Naphthalen-1-ylcarbamoyl)-hexahydro-pyrrolo[3,2-b]pyrrole-1,4-dicarboxylic acid 1-benzyl ester 4-tert-butyl ester

HRID 446986Notes

Reaction equation

HRID 446986 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH:15]2[CH:11]([N:12]([C:19]([O:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[O:20])[CH2:13][CH:14]2[C:16]([OH:18])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[NH2:60][C:61]1[C:70]2[C:65](=[CH:66][CH:67]=[CH:68][CH:69]=2)[CH:64]=[CH:63][CH:62]=1>CN1C(=O)CCC1.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH:15]2[CH:11]([N:12]([C:19]([O:21][CH2:22][C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)=[O:20])[CH2:13][CH:14]2[C:16](=[O:18])[NH:60][C:61]2[C:70]3[C:65](=[CH:66][CH:67]=[CH:68][CH:69]=3)[CH:64]=[CH:63][CH:62]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 86401-NaphthylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67216716Hexahydro-pyrrolo[3,2-b]pyrrole-1,3,4-tricarboxylic acid 1-benzyl ester 4-tert-butyl ester

Product 1

HCID 672810263-(Naphthalen-1-ylcarbamoyl)-hexahydro-pyrrolo[3,2-b]pyrrole-1,4-dicarboxylic acid 1-benzyl ester 4-tert-butyl esterYield 95%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of 36 (390 mg, 1.00 mmol) in NMP (5 mL) was cooled to 0° C. and treated with HATU (420 mg, 1.10 mmol) and NMM (0.17 mL, 1.50 mmol) followed in 15 min by the addition of 1-aminonaphthalene (145 mg, 1.00 mmol). The reaction mixture was allowed to warm to ambient temperature. After 3 h, the solution was diluted with EtOAc, washed with H2O, 1M HCl, H2O, sat NaHCO3, brine, dried over anhydrous Na2SO4, filtered and concentrated. Purification by reverse phase HPLC (2″ Dynamax® C18, 10-70% ACN in H2O with 0.1% HOAc over 30 min) afforded 53 (490 mg) as a white foam. 1H NMR (CDCl3, 300 MHz), ˜2:1 mixture of rotomers: δ8.32 (d, J=8.4 Hz, 1H), 8.15 (d, J=7.80 Hz, 1H), 7.84 (m, 1H), 7.64 (d, J=8.40 Hz, 1H), 7.42-7.56 (m, 4H), 7.26-7.42 (m, 4H), 5.17 (br s, 2H), 4.62 (m, 2H), 4.48 (dd, J=11.6, 2.5 Hz, 1H), 3.30-3.70 (m, 5H), 2.0-2.20 (m, 2H), 1.55 (s, 9H) ppm. Mass spectrum, m/z [516.1] (M+H)+.

Workup

  1. washwashed with H2O, 1M HCl, H2O
  2. dry with materialdried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by reverse phase HPLC (2″ Dynamax® C18, 10-70% ACN in H2O with 0.1% HOAc over 30 min)

Sources & evidence

ORD record
ord-67fa8138e3b44d008733353f7f5e2bee
Source dataset
uspto-grants-2013_07
Patent number
US08481495B2

Reaction notes

Loading…