Diisopropylethylamine → HCID 178456065, compound

HRID 1625138

Reaction equation

HRID 1625138 reaction equation
[NH2:1][C@H:2]([C:5]1[N:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:13](=[O:21])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][C:11]=2[F:22])[N:6]=1)[CH2:3][CH3:4].Br[C:24]1[N:32]=[CH:31][N:30]=[C:29]2[C:25]=1[NH:26][CH:27]=[N:28]2.CCN(C(C)C)C(C)C>C(O)(C)(C)C.CCO>[F:22][C:11]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:12]=1[C:13](=[O:21])[N:14]([C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)[C:5]([C@@H:2]([NH:1][C:24]1[N:32]=[CH:31][N:30]=[C:29]3[C:25]=1[N:26]=[CH:27][NH:28]3)[CH2:3][CH3:4])=[N:6]2

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 5287830Purine, 6-bromo-HCID 598410522-[(1S)-1-Aminopropyl]-5-fluoro-3-phenyl-4(3H)-quinazolinone

Product 1

HCID 178456065HCID 178456065, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of compound 111 (65.6 mmol, 1 eq), 6-bromopurine (14.6 g, 73.4 mmol, 1.1 eq), and DIEA (24.3 mL, 140 mmol, 2 eq) in tert-butanol (40 mL) was stirred for 24 h at 80° C. The reaction mixture was concentrated in vacuo and treated with water to yield a solid crude product that was collected by vacuum filtration, washed with water, and air dried. Half of the obtained solid crude product was dissolved in MeOH (600 mL), concentrated onto silica gel (300 mL dry), and purified by flash chromatography (7.5×36 cm, eluted with 10 L of 4% MeOH/CH2Cl2) to yield a solid product. The solid product was then dissolved in EtOH (250 mL) and concentrated in vacuo to compound 107 as a light yellow solid (7.2 g, 50%). 1H NMR (300 MHz, 80° C., DMSO-d6) δ 12.66 (broad s, 1H), 8.11 (s, 1H), 8.02 (broad s, 1H), 7.81-7.73 (m, 1H), 7.60-7.42 (m, 6H), 7.25-7.15 (m, 2H), 4.97 (broad s, 1H), 2.02-1.73 (m, 2H), 0.79 (t, J=7.3 Hz, 3H). ESI-MS m/z 416.2 (MH+). C, H, N elemental analysis (C22H18N7OF.EtOH.0.4 H2O). Chiral purity 99.8:0.2 (S:R) using chiral HPLC (4.6×250 mm Chiralpak ODH column, 20° C., 85:15 hexanes:EtOH, 1 mL/min, sample loaded at a concentration of 1 mg/mL in EtOH). The reaction described above and compound 107 are shown below.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additiontreated with water
  3. customto yield a solid crude product that
  4. filtrationwas collected by vacuum filtration
  5. washwashed with water, and air
  6. customdried
  7. dissolutionHalf of the obtained solid crude product was dissolved in MeOH (600 mL)
  8. concentrationconcentrated onto silica gel (300 mL dry)
  9. custompurified by flash chromatography (7.5×36 cm, eluted with 10 L of 4% MeOH/CH2Cl2)
  10. customto yield a solid product
  11. concentrationconcentrated in vacuo to compound 107 as a light yellow solid (7.2 g, 50%)
  12. custom4.6×250 mm Chiralpak ODH column, 20° C., 85:15 hexanes

Sources & evidence

ORD record
ord-73cfbb3c4f5542579605086ce5e63665
Source dataset
uspto-grants-2014_07
Patent number
US08779131B2

Linked notes

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