Diisopropylethylamine → N-(4-(6-methylpyridin-3-yloxy)-3-methylphenyl)-6-(5-((4-methyl-1,4-azaphosphinan-1-yl)methyl)furan-2-yl)quinazolin-4-amine

HRID 877098Notes

Reaction equation

HRID 877098 reaction equation
[CH3:1][C:2]1[N:7]=[CH:6][C:5]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]3[C:25]4[C:20](=[CH:21][CH:22]=[C:23]([C:26]5[O:30][C:29]([CH:31]=O)=[CH:28][CH:27]=5)[CH:24]=4)[N:19]=[CH:18][N:17]=3)=[CH:11][C:10]=2[CH3:33])=[CH:4][CH:3]=1.Cl.[CH3:35][P:36]1(=O)[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]1.CCN(C(C)C)C(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.C(O)(=O)C>[CH3:1][C:2]1[N:7]=[CH:6][C:5]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]3[C:25]4[C:20](=[CH:21][CH:22]=[C:23]([C:26]5[O:30][C:29]([CH2:31][N:39]6[CH2:40][CH2:41][P:36]([CH3:35])[CH2:37][CH2:38]6)=[CH:28][CH:27]=5)[CH:24]=4)[N:19]=[CH:18][N:17]=3)=[CH:11][C:10]=2[CH3:33])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 668330534-Methyl-1,4lambda5-azaphosphinan-4-one hydrochlorideHCID 866684775-(4-(4-(6-Methylpyridin-3-yloxy)-3-methylphenylamino)quinazolin-6-yl)furan-2-carbaldehyde

Product 1

HCID 67504483N-(4-(6-methylpyridin-3-yloxy)-3-methylphenyl)-6-(5-((4-methyl-1,4-azaphosphinan-1-yl)methyl)furan-2-yl)quinazolin-4-amine

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6344DichloromethaneSolvent

Procedure

5-(4-(4-(6-methylpyridin-3-yloxy)-3-methylphenylamino)quinazolin-6-yl)furan-2-carbaldehyde, 4-methyl-1,4-azaphosphinane 4-oxide hydrogen chloride salt and DIPEA were suspended in dichloromethane (20 mL). Sequentially, acetic acid (3 drops) and sodium triacetoxyborohydride (2 equiv.) were added at room temperature. The mixture was stirred at room temperature until the starting material disappeared. The reaction was quenched with 2N NaOH aqueous solution and extracted with dichloromethane. The combined organic layer and extracts were dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by flash chromatography, eluting with 20% methanol in dichloromethane to give the desired product as yellow crystalline solid. LCMS ESI(+) m/z: 554 (M+1). 1H NMR (300 MHz, CDCl3) δ 8.71 (s, 1H), 8.47 (s, 1H), 8.18 (d, 1H), 8.12 (s, 1H), 7.77 (d, 1H), 7.69 (m, 1H), 7.60 (d, 1H), 7.28 (m, 2H), 6.99 (m, 2H), 6.51 (d, 1H), 3.83 (s, 2H), 3.73 (m, 2H), 3.24 (m, 2H), 2.95 (m, 2H), 2.51 (s, 3H), 2.27 (s, 3H), 2.04 (m, 2H), 1.58 (m, 3H).

Workup

  1. customThe reaction was quenched with 2N NaOH aqueous solution
  2. extractionextracted with dichloromethane
  3. dry with materialThe combined organic layer and extracts were dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography
  7. washeluting with 20% methanol in dichloromethane

Sources & evidence

ORD record
ord-8e3695363c5841a8a103492e9e834aaf
Source dataset
uspto-grants-2015_03
Patent number
US08987284B2

Reaction notes

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