1,2-Dichloroethane → Ammonium Hydroxide

HRID 1481836Notes

Reaction equation

HRID 1481836 reaction equation
[CH3:1][N:2]1[C@:6]2([CH2:17][C:9]3=[N:10][CH:11]=[C:12]([C:14]([OH:16])=[O:15])[CH:13]=[C:8]3[CH2:7]2)[C:5](=[O:18])[NH:4][C:3]1=[O:19].Cl.[NH2:21][C@H:22]1[CH2:27][C@@H:26]([C:28]2[C:33]([F:34])=[C:32]([F:35])[CH:31]=[C:30]([F:36])[C:29]=2[F:37])[C@@H:25]([CH3:38])[N:24]([CH2:39][C:40]([F:43])([F:42])[F:41])[C:23]1=[O:44].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.C(N(CC)C(C)C)(C)C.C(=O)(O)[O-].[Na+]>CN(C=O)C>[NH4+:2].[OH-:15].[CH3:1][N:2]1[C@:6]2([CH2:17][C:9]3=[N:10][CH:11]=[C:12]([C:14]([NH:21][C@H:22]4[CH2:27][C@@H:26]([C:28]5[C:33]([F:34])=[C:32]([F:35])[CH:31]=[C:30]([F:36])[C:29]=5[F:37])[C@@H:25]([CH3:38])[N:24]([CH2:39][C:40]([F:43])([F:42])[F:41])[C:23]4=[O:44])=[O:16])[CH:13]=[C:8]3[CH2:7]2)[C:5](=[O:18])[NH:4][C:3]1=[O:19]

Participants

9

Reactant 6

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 86707880HCID 86707880, compound2×HCID 86707881HCID 86707881, compound2×

Product 2

HCID 14923Ammonium HydroxideHCID 60202381HCID 60202381, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred mixture of (6R)-3′-methyl-2′,5′-dioxo-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-imidazolidine]-3-carboxylic acid (described in Intermediate 19, 36 mg, 0.139 mmol), (3S,5S,6R)-3-amino-6-methyl-1-(2,2,2-trifluoroethyl)-5-(2,3,5,6-tetrafluorophenyl)piperidin-2-one hydrochloride (described in Intermediate 16, 50 mg, 0.127 mmol), HOBT (25 mg, 0.165 mmol), and EDC (32 mg, 0.165 mmol) in DMF (1.5 mL) was added N,N-diisopropylethylamine (0.066 mL, 0.380 mmol), and the resulting mixture was stirred at ambient temperature for 6 h. The reaction mixture was poured into saturated aqueous sodium bicarbonate (5 mL) and extracted with EtOAc (2×10 mL). The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated in vacuo. The residue was purified by silica gel chromatography, eluting with a gradient of CH2Cl2:MeOH:NH4OH—100:0:0 to 90:10:1, to give the title compound. HRMS: m/z=602.1632 (M+1), calculated m/z=602.1633 for C26H23F7N5O4. 1H NMR (500 MHz, CDCl3) δ 8.88 (s, 1H), 8.38 (br s, 1H), 8.03 (s, 1H), 7.55 (d, 1H, J=4.9 Hz), 7.08 (m, 4.90 (m, 1H), 4.50 (m, 1H), 4.04-3.95 (m, 2H), 3.70 (d, 1H, J=18.3 Hz), 3.61 (d, 1H, J=17.3 Hz), 3.35 (m, 1H), 3.30 (d, 1H, J=18.1 Hz), 3.20 (d, 1H, J=17.6 Hz), 2.89-2.77 (m, 2H), 2.68 (s, 3H), 1.30 (d, 3H, J=6.4 Hz).

Workup

  1. extractionextracted with EtOAc (2×10 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel chromatography
  6. washeluting with a gradient of CH2Cl2

Sources & evidence

ORD record
ord-92c9197e4c8d49b4b9b6f1ae422f0bec
Source dataset
uspto-grants-2016_08
Patent number
US09409916B2

Reaction notes

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