Isopropylamine → HCID 59519081, compound

HRID 1161872Notes

Reaction equation

HRID 1161872 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][C:13]([CH3:16])([CH3:15])[CH2:12][N:11]([C:17]2[CH:18]=[C:19]3[C:24](=[CH:25][CH:26]=2)[N:23]=[C:22]([C:27]2[CH:32]=[CH:31][C:30]([F:33])=[C:29]([O:34][CH3:35])[CH:28]=2)[N:21]([CH2:36][C:37](O)=[O:38])[C:20]3=[O:40])[CH2:10][CH:9]1[CH3:41])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:42]([NH2:45])([CH3:44])[CH3:43].CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O.CCN(C(C)C)C(C)C.C([O-])(O)=O.[Na+]>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:14][C:13]([CH3:16])([CH3:15])[CH2:12][N:11]([C:17]2[CH:18]=[C:19]3[C:24](=[CH:25][CH:26]=2)[N:23]=[C:22]([C:27]2[CH:32]=[CH:31][C:30]([F:33])=[C:29]([O:34][CH3:35])[CH:28]=2)[N:21]([CH2:36][C:37](=[O:38])[NH:45][CH:42]([CH3:44])[CH3:43])[C:20]3=[O:40])[CH2:10][CH:9]1[CH3:41])=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

7

Reactant 5

HCID 6363IsopropylamineHCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 516892Sodium BicarbonateHCID 59519054HCID 59519054, compound

Product 1

HCID 59519081HCID 59519081, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-[3-Carboxymethyl-2-(4-fluoro-3-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-6-yl]-2,6,6-trimethylperhydro-1,4-diazepine-1-carboxylic acid tert-butyl ester (200 mg, 0.352 mmol), isopropylamine (208 mg, 299 uL, 3.52 mmol), 1-propanephosphonic acid cyclic anhydride (336 mg, 320 uL, 0.528 mmol) and DIPEA (135 mg, 186 uL, 1.06 mmol) were stirred at room temperature in DCM (15 mL) for 2 h. NaHCO3 (aq.) (15 mL) was added, the organic layer separated, dried (Na2SO4) and evaporated under reduced pressure. Crude product was purified by chromatography on silica gel with a gradient of DCM to DCM:MeOH (4:1, v/v) as eluent to afford 4-[2-(4-fluoro-3-methoxyphenyl)-3-(isopropylcarbamoylmethyl)-4-oxo-3,4-dihydroquinazolin-6-yl]-2,6,6-trimethylperhydro-1,4-diazepine-1-carboxylic acid tert-butyl ester (120 mg, 0.197 mmol, 56%).

Workup

  1. customthe organic layer separated
  2. dry with materialdried (Na2SO4)
  3. customevaporated under reduced pressure
  4. customCrude product was purified by chromatography on silica gel with a gradient of DCM to DCM:MeOH (4:1

Sources & evidence

ORD record
ord-a022b0617b28440785ea8193bcac4eb2
Source dataset
uspto-grants-2010_10
Patent number
US07820649B2

Reaction notes

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