4-Methylmorpholine → HCID 67092312, compound

HRID 2074101Notes

Reaction equation

HRID 2074101 reaction equation
[F:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][C:7]2[N:11]([CH:12]3[CH2:15][NH:14][CH2:13]3)[N:10]=[C:9]([C:16]3[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=3)[CH:8]=2)=[CH:4][CH:3]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.CN1CCOCC1.[NH:52]1[CH:56]=[CH:55][N:54]=[C:53]1[C:57](O)=[O:58]>CN(C=O)C.CCOCC>[F:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][C:7]2[N:11]([CH:12]3[CH2:13][N:14]([C:57]([C:53]4[NH:52][CH:56]=[CH:55][N:54]=4)=[O:58])[CH2:15]3)[N:10]=[C:9]([C:16]3[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=3)[CH:8]=2)=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 5743211H-Imidazole-2-carboxylic acidHCID 67092285HCID 67092285, compound

Product 1

HCID 67092312HCID 67092312, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

To a suspension of 4-(5-(4-fluorobenzyl)-1-(azetidin-3-yl)-1H-pyrazol-3-yl)pyridine (85 mg, 0.28 mmol) in DMF (3 mL) was added HOBt (45 mg, 0.33 mmol), EDCI (64 mg, 0.33 mmol), NMM (76 μL, 0.69 mmol) followed by imidazole-2-carboxylic acid (34 mg, 0.30 mmol) and the mixture stirred for 16 hours at room temperature. The volatiles were removed in vacuo and the residue purified directly by Biotage flash chromatography, eluting with 2-6% MeOH/DCM to yield a clear gum. Ether was added (5 mL) and the mix sonicated to give a white precipitate that was filtered off, washed with ether and dried in-vacuo to yield the title compound as a white solid, 78 mg, 70%. 1H NMR (400 MHz, DMSO-D6) δ ppm 13.04-13.12 (m, 1 H), 8.54 (d, 2 H), 7.74 (d, 2 H), 7.25-7.32 (m, 2 H), 7.18 (t, 2 H), 7.03-7.12 (m, 1 H), 6.66 (s, 1 H), 5.33-5.46 (m, 1 H), 4.77-4.92 (m, 2 H), 4.26-4.36 (m, 2 H), 4.12 (s, 2 H); m/z (APCI+) for C22H19N6FO 403.1 (M+H)+.

Workup

  1. customThe volatiles were removed in vacuo
  2. customthe residue purified directly by Biotage flash chromatography
  3. washeluting with 2-6% MeOH/DCM
  4. customto yield a clear gum
  5. customthe mix sonicated
  6. customto give a white precipitate that
  7. filtrationwas filtered off
  8. washwashed with ether
  9. customdried in-vacuo

Sources & evidence

ORD record
ord-e53f822b039c4820926e4064a6ac9be0
Source dataset
uspto-grants-2011_04
Patent number
US07919488B2

Reaction notes

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