Ammonium Chloride → HCID 73603421, compound

HRID 593489Notes

Reaction equation

HRID 593489 reaction equation
[F:1][C:2]([F:40])([F:39])[CH2:3][CH2:4][C@@H:5]([C:16](=[O:38])[NH:17][CH:18]1[C:24](=[O:25])[NH:23][C:22]2[CH:26]=[CH:27][C:28]([O:30][CH3:31])=[CH:29][C:21]=2[C:20]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[N:19]1)[C@H:6]([CH2:10][CH2:11][C:12]([F:15])([F:14])[F:13])[C:7]([OH:9])=O.[Cl-].[NH4+].CC[N:45](C(C)C)C(C)C>CS(C)=O>[CH3:31][O:30][C:28]1[CH:27]=[CH:26][C:22]2[NH:23][C:24](=[O:25])[C@@H:18]([NH:17][C:16](=[O:38])[C@H:5]([CH2:4][CH2:3][C:2]([F:39])([F:1])[F:40])[C@H:6]([CH2:10][CH2:11][C:12]([F:15])([F:14])[F:13])[C:7]([NH2:45])=[O:9])[N:19]=[C:20]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[C:21]=2[CH:29]=1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 90087881HCID 90087881, compound

Product 1

HCID 73603421HCID 73603421, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a stirred solution of Intermediate 7E (500 mg, 1.047 mmol), pyBOP (0.65 mg, 1.25 mmol), and ammonium chloride (0.28 mg, 5.23 mmol) in DMSO (6 mL), at 0° C. under a nitrogen atmosphere, was added dropwise a solution of N,N′-diisopropylethylamine (0.36 mL, 2.09 mmol) over two minutes. The ice bath was removed and the reaction mixture was stirred at room temperature for sixteen hours. The mixture was then poured into ice cooled water (20 grams) and stirred for one hour and then filtered. The crude residue was subjected to preparative HPLC purification/separation (Column-CHIRALCEL® ODH (250×4.6) mm 5 micron, Mobile Phase A: 0.2% diethylamine-hexane (80%), Mobile Phase B: ethanol (20%), @ 220 and 250 nm Flow-1 ml/Min, Run-20 min) to provide Intermediate 7F as a white solid: yield 180 mg (10%). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.67 (s, 1H), 9.444-9.463 (d, J=7.6 Hz, 1H), 7.60-7.7 (brs, 1H), 7.51-7.54 (m, 3H), 7.44-7.47 (m, 2H), 7.24-7.28 (m, 2H), 7.14-7.19 (brs, 1H), 6.77-6.78 (d, J=4 Hz, 1H), 5.3-5.31 (d, J=4 Hz, 1H), 3.71 (s, 3H), 2.78-2.84 (m, 1H), 2.2.11-2.31 (m, 4H), 1.60-1.74 (m, 4H), MS (M−1)=571. HPLC RT=9.31 min (Xbridge Phenyl (4.6×150 mm), 3.5 micron; 1 mL/min flow rate; gradient 10% B-100% B over 12 min (A: 0.05% TFA in water/CH3CN (95:5), B: 0.05% TFA in water/CH3CN (5:95) @ 220 and 250 nm, 15 min run).

Workup

  1. customThe ice bath was removed
  2. additionThe mixture was then poured into ice
  3. temperaturecooled water (20 grams)
  4. stirringstirred for one hour
  5. filtrationfiltered
  6. customThe crude residue was subjected to preparative HPLC purification/separation (Column-CHIRALCEL® ODH (250×4.6) mm 5 micron, Mobile Phase A: 0.2% diethylamine-hexane (80%), Mobile Phase B: ethanol (20%), @ 220 and 250 nm Flow-1 ml/Min, Run-20 min)

Sources & evidence

ORD record
ord-23787088974d4559abb7d5e44da0c72d
Source dataset
uspto-grants-2016_01
Patent number
US09242940B2

Reaction notes

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