Dimethylformamide → HCID 66767280, compound

HRID 2195552Notes

Reaction equation

HRID 2195552 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[O:9][C:10]1[C:18]([N:19]2[CH2:24][CH2:23][O:22][CH:21]([CH3:25])[CH2:20]2)=[CH:17][C:16]2[C:12](=[CH:13][N:14]([CH:26]3[CH2:31][CH2:30][CH2:29][CH2:28][O:27]3)[N:15]=2)[CH:11]=1)[NH2:5].[F:32][C:33]1[CH:38]=[CH:37][C:36]([N:39]2[CH:44]=[CH:43][CH:42]=[C:41]([C:45]([OH:47])=[O:46])[C:40]2=[O:48])=[CH:35][CH:34]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CN(C=O)C.CCN(C(C)C)C(C)C>CCOC(C)=O>[F:1][C:2]1[CH:3]=[C:4]([NH:5][C:45]([C:41]2[C:40](=[O:48])[N:39]([C:36]3[CH:35]=[CH:34][C:33]([F:32])=[CH:38][CH:37]=3)[CH:44]=[CH:43][CH:42]=2)=[O:46])[CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][C:18]=1[N:19]1[CH2:24][CH2:23][O:22][CH:21]([CH3:25])[CH2:20]1)[NH:15][N:14]=[CH:13]2.[F:1][C:2]1[CH:3]=[C:4]([NH:5][C:45]([C:41]2[C:40](=[O:48])[N:39]([C:36]3[CH:35]=[CH:34][C:33]([F:32])=[CH:38][CH:37]=3)[CH:44]=[CH:43][CH:42]=2)=[O:47])[CH:6]=[CH:7][C:8]=1[O:9][C:10]1[C:18]([N:19]2[CH2:24][CH2:23][O:22][CH:21]([CH3:25])[CH2:20]2)=[CH:17][C:16]2[C:12](=[CH:13][N:14]([CH:26]3[CH2:31][CH2:30][CH2:29][CH2:28][O:27]3)[N:15]=2)[CH:11]=1

Participants

9

Reactant 6

HCID 6228DimethylformamideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 210815271-(4-Fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acidHCID 66766865HCID 66766865, compound

Product 2

HCID 59159912HCID 59159912, compoundHCID 66767280HCID 66767280, compoundYield 211.5%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a 10 mL screw-cap vial is added 3-fluoro-4-(6-(2-methylmorpholino)-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-5-yloxy)aniline (44 mg, 103.17 μmol), 1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid (42 mg, 0.18 mmol), EDCI (45.177 mg, 232.13 μmol), HOBT (23.699 mg, 154.75 μmol) followed by DMF (5 mL, 64.66 mmol) and DIPEA (44.980 μL, 257.92 μmol). The reaction mixture is stirred at RT overnight. The reaction is diluted into EtOAc (50 mL) and washed with saturated aqueous sodium chloride (5×25 mL). Organic layers are dried over Na2SO4, filtered, and concentrated to dryness. The residue is purified on a silica gel column eluting with hexanes (A) and EtOAc (B), gradient from 80% (A): 20% (B) to 30% (A): 70% (B) over 40 min, hold at 30:70 ratio for 15 min to give a yellow solid as desired product N-(3-fluoro-4-(6-(2-methylmorpholino)-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-5-yloxy)phenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (70 mg, 99% yield). MS (m/z): 641.8 (M+H).

Workup

  1. customTo a 10 mL screw-cap vial
  2. washwashed with saturated aqueous sodium chloride (5×25 mL)
  3. dry with materialOrganic layers are dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. customThe residue is purified on a silica gel column
  7. washeluting with hexanes (A) and EtOAc (B), gradient from 80% (A)
  8. wait20% (B) to 30% (A): 70% (B) over 40 min
  9. waithold at 30:70 ratio for 15 min

Sources & evidence

ORD record
ord-4a180b9ddab5414e8ee73d1ec643bac1
Source dataset
uspto-grants-2012_12
Patent number
USRE043878E1

Reaction notes

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