Acetic Acid → HCID 71573264, compound

HRID 712420Notes

Reaction equation

HRID 712420 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:32][CH3:33])=[C:17]([O:20][CH2:21][CH2:22][CH2:23][N:24]4[CH2:31][CH:30]5[CH:26]([CH2:27][NH:28][CH2:29]5)[CH2:25]4)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8].C=O.[CH3:36]C(O)=O>C(Cl)Cl.CO.O>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:32][CH3:33])=[C:17]([O:20][CH2:21][CH2:22][CH2:23][N:24]4[CH2:31][CH:30]5[CH:26]([CH2:27][N:28]([CH3:36])[CH2:29]5)[CH2:25]4)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

7

Reactant 3

HCID 176Acetic AcidHCID 712FormaldehydeHCID 86729475HCID 86729475, compound

Product 1

HCID 71573264HCID 71573264, compoundYield 68%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of N-(3-chloro-4-fluorophenyl)-6-(3-(hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl) propoxy)-7-methoxyquinazolin-4-amine (0.20 g) in a mixture of CH2Cl2 and MeOH was added 37% HCHO (0.10 mL), AcOH (0.15 mL) and NaB(O2CCH3)3H (0.26 g) in turn. The mixture was stirred for 1.5 h, then diluted with water and extracted with CH2Cl2. The organic layer was dried over anhydrous Na2SO4 for 1 h and filtered. The filtrate was concentrated and redissolved in EA, to this, a solution of HCl in EtOAc (10 mL) was added under stifling. The mixture was filtered to give the title compound as a solid (0.13 g, 68.00%), HPLC: 98.69%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 486.2 (M+1); 1H NMR (400 MHz, CDCl3) δ: 1.81-1.92 (m, 4H), 2.10-2.15 (m, 4H), 2.30 (s, 3H), 2.35-2.41 (m, 4H), 2.44 (t, J=8.2 Hz, 2H), 4.03 (s, 3H), 4.10 (t, J=7.8 Hz, 2H), 7.16 (s, 1H), 7.26 (s, 1H), 7.45 (s, 1H), 7.57-7.62 (m, 1H), 7.91-7.93 (m, 1H), 8.64 (s, 1H) ppm.

Workup

  1. extractionextracted with CH2Cl2
  2. dry with materialThe organic layer was dried over anhydrous Na2SO4 for 1 h
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated
  5. dissolutionredissolved in EA
  6. additionto this, a solution of HCl in EtOAc (10 mL) was added under stifling
  7. filtrationThe mixture was filtered

Sources & evidence

ORD record
ord-49d95caf702a48a1b1f6a8a0767b90c3
Source dataset
uspto-grants-2015_11
Patent number
US09181277B2

Reaction notes

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