Formaldehyde → HCID 71572548, compound

HRID 712428Notes

Reaction equation

HRID 712428 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:40][CH3:41])=[C:17]([O:20][CH2:21][CH2:22][CH2:23][N:24]4[CH2:29][CH2:28][CH:27]5[CH2:30][CH2:31][N:32]([C:33](OC(C)(C)C)=O)[CH:26]5[CH2:25]4)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8].C(Cl)Cl.CO.C=O>O.CC(O)=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:40][CH3:41])=[C:17]([O:20][CH2:21][CH2:22][CH2:23][N:24]4[CH2:29][CH2:28][CH:27]5[CH2:30][CH2:31][N:32]([CH3:33])[CH:26]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 4

HCID 712FormaldehydeHCID 887MethanolHCID 6344DichloromethaneHCID 86729479HCID 86729479, compound

Product 1

HCID 71572548HCID 71572548, compoundYield 76.2%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

To a solution of tert-butyl 6-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy) propyl)octahydro-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (0.20 g) in the mixture solvent of CH2Cl2 and MeOH was added 37% HCHO (0.10 mL), AcOH (0.15 mL) and NaB(O2CCH3)3H (0.26 g) in turn at room temperature. The mixture was stirred for 1.5 h, 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 stirring. The mixture was filtered to give the title compound as a solid (0.13 g, 68.00%), HPLC: 98.22%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 500.2 (M+1); 1H NMR (400 MHz, CDCl3) δ: 1.45 (m, 2H), 1.68 (m, 3H), 1.80 (m, 2H), 2.10 (m, 1H), 2.22 (m, 5H), 2.25 (s, 3H), 2.42 (m, 3H), 4.03 (s, 3H), 4.10 (m, 2H), 6.76 (s, 1H), 7.16 (d, J=8.2 Hz, 1H), 7.24 (s, 1H), 7.28 (d, J=8.0 Hz, 1H), 7.41 (s, 1H), 8.54 (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
  7. stirringunder stirring
  8. filtrationThe mixture was filtered

Sources & evidence

ORD record
ord-c8291b66ec644b9fb447dcd3bfe8c462
Source dataset
uspto-grants-2015_11
Patent number
US09181277B2

Reaction notes

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