4-Methylmorpholine → HCID 67358657, compound

HRID 1667193Notes

Reaction equation

HRID 1667193 reaction equation
[CH2:1]([N:8]1[CH2:16][CH2:15][C:11]2([CH2:14][NH:13][CH2:12]2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2([C:34]3[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=3)[CH2:28][CH2:27][N:26]([CH2:29][C:30](O)=[O:31])[C:25]2=[O:33])=[CH:20][CH:19]=1.C(N=C=NCCCN(C)C)C.CN1CCOCC1>ClCCl>[CH2:1]([N:8]1[CH2:9][CH2:10][C:11]2([CH2:14][N:13]([C:30](=[O:31])[CH2:29][N:26]3[CH2:27][CH2:28][C:24]([C:21]4[CH:22]=[CH:23][C:18]([F:17])=[CH:19][CH:20]=4)([C:34]4[CH:35]=[CH:36][C:37]([F:40])=[CH:38][CH:39]=4)[C:25]3=[O:33])[CH2:12]2)[CH2:15][CH2:16]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 441823467-Benzyl-2,7-diazaspiro[3.5]nonaneHCID 673571912-(3,3-Bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl)acetic acid

Product 1

HCID 67358657HCID 67358657, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

7-Benzyl-2,7-diazaspiro[3.5]nonane (0.237 g, 0.749 mmol), 2-(3,3-bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl)acetic acid (0.248 g, 0.749 mmol; Example 58D), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine (0.199 mL, 1.123 mmol) and N-methylmorpholine (0.247 mL, 2.247 mmol) were stirred together in dichloromethane (2 mL). After stirring overnight, the reaction was diluted with dichloromethane (20 mL) and washed with 1 N HCl (10 mL) and brine (10 mL), dried over magnesium sulfate and concentrated. The residue was loaded onto a GraceResolv™ 40 g silica gel column (Grace Davison Discovery Sciences) and the title compound eluted with a gradient of 0.4% methanol/dichloromethane containing 0.2 N NH3 to 6% methanol/dichloromethane containing 0.2 N NH3 (Flow=40 mL/minute) over 40 minutes. 1H NMR (300 MHz, CDCl3) δ 7.39-7.15 (m, 9H), 6.99 (t, J=8.2, 4H), 3.97 (s, 2H), 3.72 (d, J=20.0, 4H), 3.53 (t, J=6.5, 2H), 3.46 (s, 2H), 2.75 (t, J=6.4, 2H), 2.32 (s, 4H), 1.73 (s, 4H); MS (ESI+) m/z 530.2 (M+H)+.

Workup

  1. washwashed with 1 N HCl (10 mL) and brine (10 mL)
  2. dry with materialdried over magnesium sulfate
  3. concentrationconcentrated
  4. washthe title compound eluted with a gradient of 0.4% methanol/dichloromethane containing 0.2 N NH3 to 6% methanol/dichloromethane containing 0.2 N NH3 (Flow=40 mL/minute) over 40 minutes

Sources & evidence

ORD record
ord-b576699bdcba4517a239e48464397315
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

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