Formaldehyde → HCID 71572440, compound

HRID 712458Notes

Reaction equation

HRID 712458 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:33][CH3:34])=[C:17]([O:20][CH2:21][CH2:22][CH2:23][N:24]4[CH2:29][CH2:28][CH2:27][CH:26]5[CH2:30][NH:31][CH2:32][CH:25]45)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8].CO.[CH2:37](Cl)Cl.C=O>O.C(O)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:33][CH3:34])=[C:17]([O:20][CH2:21][CH2:22][CH2:23][N:24]4[CH2:29][CH2:28][CH2:27][CH:26]5[CH2:30][N:31]([CH3:37])[CH2:32][CH:25]45)[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 71572439HCID 71572439, compound

Product 1

HCID 71572440HCID 71572440, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

To a solution of N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-(octahydro-1H-pyrrolo[3,4-b]pyridin-1-yl) propoxy)quinazolin-4-amine (0.45 g) in the mixture solvent of MeOH and CH2Cl2 (1:1) was added 37% HCHO (1.00 mL) and acetic acid (0.50 mL) dropwise. The reaction mixture was stirred for 30 min at room temperature, NaB(OCOCH3)3H (1.50 g) was added in portions. The reaction mixture was stirred for another 2 h at room temperature, poured into water and extracted with CH2Cl2 (50 mL×3). The combined organic phases were dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was chromatographed with a silica gel column (eluting agent: 20:1 (v/v) DCM/MeOH) to give the title compound as a pale yellow solid (0.60 g, 70.00%), HPLC: 98.00%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 500.1 (M+1); 1H NMR (400 MHz, d6-DMSO) δ: 1.82 (m, 1H), 2.33 (m, 4H), 1.94 (m, 1H), 2.19-2.20 (m, 2H), 2.50-2.52 (m, 1H), 2.67-2.70 (m, 2H), 3.58 (s, 3H), 4.01-4.02 (m, 2H), 4.03-4.04 (m, 5H), 4.05-4.07 (m, 1H), 4.40 (s, 2H), 7.44 (s, 1H), 7.50 (t, J=4.8 Hz, 1H), 7.83-7.88 (m, 1H), 8.07-8.08 (m, 1H), 8.89-8.91 (m, 1H), 9.05 (s, 1H) ppm.

Workup

  1. stirringThe reaction mixture was stirred for another 2 h at room temperature
  2. extractionextracted with CH2Cl2 (50 mL×3)
  3. dry with materialThe combined organic phases were dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue was chromatographed with a silica gel column (eluting agent: 20:1 (v/v) DCM/MeOH)

Sources & evidence

ORD record
ord-160dcb8d296e45f6b488a5f7c1bc2431
Source dataset
uspto-grants-2015_11
Patent number
US09181277B2

Reaction notes

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