Tert-Butylamine → HCID 59518960, compound

HRID 1161874Notes

Reaction equation

HRID 1161874 reaction equation
[N:1]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[N:4]([C:10]1[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=1)[N:16]=[C:15]([C:20]1[CH:25]=[CH:24][C:23]([F:26])=[C:22]([O:27][CH3:28])[CH:21]=1)[N:14]([CH2:29][C:30]([OH:32])=O)[C:13]3=[O:33])[CH2:3][CH2:2]2.[C:34]([NH2:38])([CH3:37])([CH3:36])[CH3:35].C(N(CC)C(C)C)(C)C.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>C(Cl)Cl.CO>[C:34]([NH:38][C:30](=[O:32])[CH2:29][N:14]1[C:13](=[O:33])[C:12]2[C:17](=[CH:18][CH:19]=[C:10]([N:4]3[CH:5]4[CH2:6][CH2:7][N:1]([CH2:9][CH2:8]4)[CH2:2][CH2:3]3)[CH:11]=2)[N:16]=[C:15]1[C:20]1[CH:25]=[CH:24][C:23]([F:26])=[C:22]([O:27][CH3:28])[CH:21]=1)([CH3:37])([CH3:36])[CH3:35]

Participants

7

Reactant 4

HCID 6385Tert-ButylamineHCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 67416387HCID 67416387, compound

Product 1

HCID 59518960HCID 59518960, compoundYield 33%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

[6-(1,4-Diazabicyclo[3.2.2]non-4-yl)-2-(4-fluoro-3-methoxyphenyl)-4-oxo-4H-quinazolin-3-yl]acetic acid (INTERMEDIATE IX.7) (20 mg, 0.44 mmol) was dissolved in DCM (5 mL). Tert-butylamine (6.5 mg, 0.088 mmol) and N,N-diisopropylethylamine (7 mg, 0.053 mmol) were added followed by 1-propanephosphonic acid cyclic anhydride (21 mg, 0.02 mL, 0.066 mmol). The reaction mixture was stirred at room temperature for 12 h. Methanol (5 mL) was added and the solution poured directly onto an SCX cartridge. Elution with 2N NH3/MeOH followed further purification by preparative HPLC afforded N-tert-butyl-2-[6-(1,4-diazabicyclo[3.2.2]non-4-yl)-2-(4-fluoro-3-methoxyphenyl)-4-oxo-4H-quinazolin-3-yl]acetamide (EXAMPLE 9a) (7.3 mg, 0.014 mmol, 33%).

Workup

  1. additionthe solution poured directly onto an SCX cartridge
  2. washElution with 2N NH3/MeOH
  3. custompurification by preparative HPLC

Sources & evidence

ORD record
ord-a2b4d52005e84a0abca7c3158c165a70
Source dataset
uspto-grants-2010_10
Patent number
US07820649B2

Reaction notes

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