Cycloheptylamine → HCID 69023440, compound

HRID 1866497Notes

Reaction equation

HRID 1866497 reaction equation
[Si:1]([O:8][C@H:9]([C:25]1[CH:30]=[CH:29][C:28]([OH:31])=[C:27]([CH2:32][OH:33])[CH:26]=1)[CH2:10][NH:11][C@H:12]([CH3:24])[CH2:13][C:14]1[CH:15]=[C:16]([CH2:20][C:21](O)=[O:22])[CH:17]=[CH:18][CH:19]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Cl.CN(C)CCCN=C=NCC.O.OC1C2N=NNC=2C=CC=1.C(N(CC)CC)C.[CH:64]1([NH2:71])[CH2:70][CH2:69][CH2:68][CH2:67][CH2:66][CH2:65]1>CN(C)C=O>[NH3:11].[Si:1]([O:8][C@H:9]([C:25]1[CH:30]=[CH:29][C:28]([OH:31])=[C:27]([CH2:32][OH:33])[CH:26]=1)[CH2:10][NH:11][C@H:12]([CH3:24])[CH2:13][C:14]1[CH:15]=[C:16]([CH2:20][C:21]([NH:71][CH:64]2[CH2:70][CH2:69][CH2:68][CH2:67][CH2:66][CH2:65]2)=[O:22])[CH:17]=[CH:18][CH:19]=1)([C:4]([CH3:6])([CH3:7])[CH3:5])([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 2899CycloheptylamineHCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 58959819(3-{(2R)-2-[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino]-propyl}-phenyl)-acetic acidHCID 178526939HCID 178526939, compound

Product 2

HCID 222AmmoniaHCID 69023440HCID 69023440, compoundYield 117.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of (3-{(2R)-2-[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino]-propyl}-phenyl)-acetic acid (Preparation 20) (250 mg, 0.45 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (94 mg, 0.49 mmol), hydroxybenzotriazole monohydrate (66 mg, 0.49 mmol) in N,N-dimethylformamide (4 ml) was treated with triethylamine (0.12 ml, 0.89 mmol) and cycloheptylamine (56 mg, 0.49 mmol) and the resulting suspension left to stir at room temperature under a nitrogen atmosphere for 18 hours. The solvent was removed in vacuo and the residue partitioned between ethyl acetate (10 ml) and saturated aqueous sodium bicarbonate (10 ml). The organic phase was separated, and the aqueous phase extracted with further ethyl acetate (2×10 ml). The combined organic extracts were washed with water (5 ml), brine (5 ml), dried (sodium sulfate) and the solvent removed in vacuo. The residue was purified by flash column chromatography on silica gel eluting with dichloromethane:methanol:880 ammonia (95:5:0.5 by volume) to give the title compound as a pale yellow oil (150 mg). 1H NMR (400 MHz, CD3OD): δ=7.20-6.98 (6H, m), 6.68 (1H, d), 4.60 (3H, m), 3.80 (1H, m), 3.40 (2H, s), 2.85 (2H, m), 2.63 (2H, m), 2.58 (1H, m), 1.80 (2H, m), 1.75-1.40 (10H, m), 1.03 (3H, d), 0.83 (9H, s), 0.00 (3H, s), −0.20 (3H, s) ppm. LRMS (electrospray): m/z [M+H]+ 569.

Workup

  1. waitthe resulting suspension left
  2. customThe solvent was removed in vacuo
  3. customthe residue partitioned between ethyl acetate (10 ml) and saturated aqueous sodium bicarbonate (10 ml)
  4. customThe organic phase was separated
  5. extractionthe aqueous phase extracted with further ethyl acetate (2×10 ml)
  6. washThe combined organic extracts were washed with water (5 ml), brine (5 ml)
  7. dry with materialdried (sodium sulfate)
  8. customthe solvent removed in vacuo
  9. customThe residue was purified by flash column chromatography on silica gel eluting with dichloromethane

Sources & evidence

ORD record
ord-9e11db20feca430aad4388904219bb70
Source dataset
uspto-grants-2009_12
Patent number
US07629358B2

Reaction notes

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