4-Methylmorpholine → HCID 18661240, compound

HRID 965133Notes

Reaction equation

HRID 965133 reaction equation
CN1CCOCC1.Cl.[NH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][OH:17].[C:18]([O:22][C:23]([NH:25][C@H:26]([C:37](O)=[O:38])[CH2:27][C:28]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[NH:30][CH:29]=1)=[O:24])([CH3:21])([CH3:20])[CH3:19].ON1C2C=CC=CC=2N=N1.CCN=C=NCCCN(C)C.Cl>CN(C=O)C>[OH:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][NH:9][C:37](=[O:38])[C@H:26]([CH2:27][C:28]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[NH:30][CH:29]=1)[NH:25][C:23]([O:22][C:18]([CH3:21])([CH3:19])[CH3:20])=[O:24]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 83169N-tert-Butoxycarbonyl-L-tryptophanHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 19367513168681-46-7

Product 1

HCID 18661240HCID 18661240, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-Methylmorpholine (2.2 mL, 19.7 mmol) was added dropwise at room temperature to 7-amino-1-heptanol hydrochloride salt (3.3 g, 19.7 mmol), in 50 mL of dry DMF under argon with stirring. After stirring for 5 minutes the following were added: N-t-butoxycarbonyl-L-tryptophan, (5 g, 16.45 mmol), 1-hydroxybenzotriazole, (2.52 g, 16.45 mmol) and EDCI hydrochloride (4.73 g, 24.7 mmol). The mixture was stirred for 2 hours and then the DMF removed under reduced pressure. The residue was taken up in cold 2.5% HCl (100 mL) and ethyl acetate (3×100 mL) and transferred to a separatory funnel. The organic phase was isolated and washed consecutively with cold 2.5% HCl (100 mL) and then brine (100 mL). The ethyl acetate phase was dried (MgSO4), filtered and concentrated to obtain N-t-butoxycarbonyl-L-tryptophan-(7-hydroxyheptyl)amide; IR (neat): 3300, 2921, 1685, 1645, 1490, 1356, 1157 cm-1 ; 1H NMR (80 MHz, CDCl3): δ0.98-1.62 (m, 10H, --(CH2)5 --), 1.45 (s, 9H, t-butyl), 2.86-3.32 (m, 4H,CH--CH2, HN--CH2), 3.68 (t, 2H, J=5.6 Hz, --CH2OH), 4.22-4.55 (m, 1H, CH), 5.12-5.32 (broad d, 1H, NH--CH), 5.65-5.9 (broad t, 1H, NH--CH2), 6.98-7.92 (m, 5H, ArH), 8.63 (broad s, indole NH).

Workup

  1. stirringAfter stirring for 5 minutes the
  2. additionfollowing were added
  3. stirringThe mixture was stirred for 2 hours
  4. customthe DMF removed under reduced pressure
  5. customtransferred to a separatory funnel
  6. customThe organic phase was isolated
  7. washwashed consecutively with cold 2.5% HCl (100 mL)
  8. dry with materialThe ethyl acetate phase was dried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-1b346d0868c34299a32edaafcab8cbc9
Source dataset
uspto-grants-1998_06
Patent number
US05773428

Reaction notes

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