Morpholine → HCID 86715496, compound

HRID 2284588Notes

Reaction equation

HRID 2284588 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]3[CH:15]=[C:16]4[C:20](=[C:21]([C:23](O)=[O:24])[CH:22]=3)[NH:19][N:18]=[CH:17]4)=[CH:12][CH:11]=[CH:10][N:9]=2)=[CH:4][C:3]=1[CH3:26].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH:51]1[CH2:56][CH2:55][O:54][CH2:53][CH2:52]1.CCN(CC)CC>C(#N)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]3[CH:15]=[C:16]4[C:20](=[C:21]([C:23]([N:51]5[CH2:56][CH2:55][O:54][CH2:53][CH2:52]5)=[O:24])[CH:22]=3)[NH:19][N:18]=[CH:17]4)=[CH:12][CH:11]=[CH:10][N:9]=2)=[CH:4][C:3]=1[CH3:26]

Participants

6

Reactant 4

HCID 8083MorpholineHCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86715495HCID 86715495, compound

Product 1

HCID 86715496HCID 86715496, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A capped vial containing a stir-bar, was charged with 5-(2-(4-fluoro-3-methylphenyl)pyridin-3-yl)-1H-indazole-7-carboxylic acid (100 mg, 0.28 mmol), HBTU (140 mg, 0.36 mmol), morpholine (29 mg, 0.03 mL, 0.34 mmol), NEt3 (57 mg, 0.08 mL, 0.57 mmol) and acetonitrile (3 ml) successively and stirred the contents at room temperature. After 12 h, the reaction mixture was concentrated and diluted with EtOAc (15 mL)/H2O (5 mL). Organic layer was separated, washed with brine, dried over anhydrous Na2SO4, concentrated and purified by preparative HPLC. Product fractions were concentrated, diluted with water and neutralized with aq. Na2CO3 solution. The resulting white precipitate was filtered and dried to obtain (5-(2-(4-fluoro-3-methylphenyl)pyridin-3-yl)-1H-indazol-7-yl)(morpholino)methanone. 1H NMR (DMSO-d6): δ 13.27 (s, 1H), 8.66 (d, 1H, J=4.7 Hz), 8.17 (s, 1H), 7.97-7.92 (m, 2H), 7.48 (dd, 1H, J=4.9 and 7.6 Hz), 7.33 (d, 1H, J=7.8 Hz), 6.97-6.88 (m, 3H), 3.62-3.42 (m, 8H), 2.10 (s, 3H).19F NMR (DMSO-d6): δ −118.69 (s).LCMS: rt 4.45 min (A), purity 97%, MS (m/e) 417 (MH+)

Workup

  1. additionA capped vial containing a stir-bar
  2. concentrationthe reaction mixture was concentrated
  3. additiondiluted with EtOAc (15 mL)/H2O (5 mL)
  4. customOrganic layer was separated
  5. washwashed with brine
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated
  8. custompurified by preparative HPLC
  9. concentrationProduct fractions were concentrated
  10. additiondiluted with water and neutralized with aq. Na2CO3 solution
  11. filtrationThe resulting white precipitate was filtered
  12. customdried

Sources & evidence

ORD record
ord-98e94fa602ff4cbeb56014437e5f1ad8
Source dataset
uspto-grants-2015_09
Patent number
US09145433B2

Reaction notes

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