Acetic Acid → HCID 49855668, compound

HRID 877083Notes

Reaction equation

HRID 877083 reaction equation
[NH2:1][CH2:2][CH2:3][P:4](=[O:9])([O:7][CH3:8])[O:5][CH3:6].[F:10][C:11]1[CH:12]=[C:13]([CH:41]=[CH:42][CH:43]=1)[CH2:14][O:15][C:16]1[CH:21]=[CH:20][C:19]([NH:22][C:23]2[C:32]3[C:27](=[CH:28][CH:29]=[C:30]([C:33]4[O:37][C:36]([CH:38]=O)=[CH:35][CH:34]=4)[CH:31]=3)[N:26]=[CH:25][N:24]=2)=[CH:18][C:17]=1[Cl:40].CCN(C(C)C)C(C)C.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[OH-].[Na+]>ClCCCl>[Cl:40][C:17]1[CH:18]=[C:19]([NH:22][C:23]2[C:32]3[C:27](=[CH:28][CH:29]=[C:30]([C:33]4[O:37][C:36]([CH2:38][NH:1][CH2:2][CH2:3][P:4](=[O:9])([O:7][CH3:8])[O:5][CH3:6])=[CH:35][CH:34]=4)[CH:31]=3)[N:26]=[CH:25][N:24]=2)[CH:20]=[CH:21][C:16]=1[O:15][CH2:14][C:13]1[CH:41]=[CH:42][CH:43]=[C:11]([F:10])[CH:12]=1

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 11181296(5-(4-(4-((3-Fluorobenzyl)oxy)-3-chloroanilino)-6-quinazolinyl)-2-furancarboxaldehydeHCID 53683450HCID 53683450, compound

Product 1

HCID 49855668HCID 49855668, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a suspension of compound 6.2 (153 mg, 1 mmol) and the compound 1.7 (473 mg, 1 mmol) in DCE (5 mL) was added DIPEA (1.5 mmol) and HOAc (1.5 mmol). After stirring the mixture for 30 minutes, 2.0 mmol of NaBH(OAc)3 was added followed by Stirring the mixture overnight. 1.0 mL of 5M NaOH was added and the mixture was extracted with DCM (2×20 mL). Combined organics was washed with brine and dried over MgSO4. Filtration and concentration followed by purification through flash column chromatography on silica gel (10% methanol in DCM) to get pale brown powder. LCMS ESI(+) m/z: 612 (M+1). 1H NMR (CD3OD, 300 MHz) δ 8.64 (s, 1H), 8.45 (s, 1H), 8.13 (d, J=8.4 Hz, 1H), 7.89 (s, 1H), 7.73 (d, J=8.4 Hz, 1H), 7.61 (d, J=7.9 Hz, 1H), 7.38 (m, 1H), 7.28 (d, J=8.8 Hz, 1H), 7.23 (d, J=5.4 Hz, 1H), 7.05 (m, 1H), 6.90 (d, J=2.7 Hz, 1H), 6.44 (d, J=2.7 Hz, 1H), 5.20 (s, 2H), 3.73 (s, 3H), 3.70 (s, 3H), 2.90 (m, 2H), 2.10 (m, 2H).

Workup

  1. stirringby Stirring the mixture overnight
  2. extractionthe mixture was extracted with DCM (2×20 mL)
  3. washCombined organics was washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationFiltration and concentration
  6. customfollowed by purification through flash column chromatography on silica gel (10% methanol in DCM)
  7. customto get pale brown powder

Sources & evidence

ORD record
ord-9fac3babb9af41dda21b542dca10b0b7
Source dataset
uspto-grants-2015_03
Patent number
US08987284B2

Reaction notes

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