Triethylamine → HCID 67302198, compound

HRID 1015351Notes

Reaction equation

HRID 1015351 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8]([N:11]1[CH2:16][CH2:15][CH:14]([CH2:17][O:18][C:19]2[CH:28]=[CH:27][CH:26]=[C:25]3[C:20]=2[C:21]([NH2:30])=[N:22][C:23]([NH2:29])=[N:24]3)[CH2:13][CH2:12]1)(=[O:10])=[O:9].N1CCC(COC2C=CC=C3C=2C(N)=NC(N)=N3)CC1.C(N(CC)CC)C.FC1C=CC=CC=1S([Cl:68])(=O)=O>CN(C)C=O.Cl.CCOCC.CO.C(Cl)Cl>[ClH:68].[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8]([N:11]1[CH2:12][CH2:13][CH:14]([CH2:17][O:18][C:19]2[CH:28]=[CH:27][CH:26]=[C:25]3[C:20]=2[C:21]([NH2:30])=[N:22][C:23]([NH2:29])=[N:24]3)[CH2:15][CH2:16]1)(=[O:10])=[O:9]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 1377612-Fluorobenzenesulphonyl chlorideHCID 25002763HCID 25002763, compound2×HCID 575765655-(Piperidin-4-ylmethoxy)quinazoline-2,4-diamine

Product 1

HCID 67302198HCID 67302198, compoundYield 85%

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

[5-(1-(2-Fluorobenzenesulfonyl)piperidin-4-ylmethoxy]quinazoline-2,4-diamine (Method CC) (Example-025). To a mixture of 5-(piperidin-4-ylmethoxy)quinazoline-2,4-diamine (250 mg; 0.9 mmol) and triethylamine (0.3 mL; 1.8 mmol) in 2.5 mL N,N-dimethylformamide was added 2-fluorobenzenesulfonyl chloride (196 mg; 1.0 mmol) and stirred at room temperature for 5 hours. Reaction was quenched with 1 mL 1N NaOH creating a homogenous mixture. After 1.5 hours, 1 mL of water was added to the newly formed precipitates and solids were collected by filtration. Solids were triturated with ethanol and rinsed once with diethyl ether to yield crude compound. (331 mg; 85% yield). 5-[1-(2-Fluorobenzenesulfonyl)piperidin-4-ylmethoxy]quinazoline-2,4-diamine (250 mg, 0.6 mmol) was purified by silica gel column (5% MeOH/CH2Cl2+1% NH4OH). The fractions were reduced to 5 mL and diluted with 2 M HCl in Et2O (5 mL). The solvents were completely removed under N2 purge. The resulting semi-solid was triturated with absolute EtOH, and stored at 2° C. for 72 hours. The resulting solids are filtered and dried under vacuum at 30° C. overnight to yield 182 mg of 5-[1-(2-fluorobenzenesulfonyl)piperidin-4-ylmethoxy]quinazoline-2,4-diamine hydrochloride. 1HNMR (500 MHz, DMSO-d6) δ 12.93 (s, 1H), 8.95 (s, 1H), 8.16 (s, 1H), 7.80 (t, J=7.5 Hz, 1H), 7.77 (dt, J=7.5, 2.5 Hz, 1H), 7.68 (t, J=8.5 Hz, 1H), 7.50 (t, J=8.5 Hz, 1H), 7.45 (t, J=7.5 Hz, 1H), 6.99 (d, J=8.5 Hz, 1H), 4.14 (d, J=6.5 Hz, 2H), 3.74 (br d, J=12.0 Hz, 2H), 2.54 (m, 2H), 2.07 (m, 1H), 1.84 (br d, J=12 Hz, 2H), 1.33 (m. 2H). 12CNMR (500 MHz, DMSO-d6) δ 162.3, 159.2, 157.2, 156.8, 154.2, 141.0, 136.2, 135.8, 130.8, 125.1, 124.2, 117.6, 117.5, 108.6, 106.8, 99.6, 73.1, 45.1, 33.4, 27.8. MS m/z (ESI) 432 (M+H)+.

Workup

  1. customReaction
  2. customwas quenched with 1 mL 1N NaOH creating a homogenous mixture
  3. waitAfter 1.5 hours
  4. addition1 mL of water was added to the
  5. customnewly formed
  6. customprecipitates
  7. filtrationsolids were collected by filtration
  8. customSolids were triturated with ethanol
  9. washrinsed once with diethyl ether
  10. customto yield crude compound
  11. customThe solvents were completely removed under N2
  12. custompurge
  13. customThe resulting semi-solid was triturated with absolute EtOH
  14. waitstored at 2° C. for 72 hours
  15. filtrationThe resulting solids are filtered
  16. customdried under vacuum at 30° C. overnight

Sources & evidence

ORD record
ord-3b072d6bb06344ef9c527f4b3ef85049
Source dataset
uspto-grants-2011_07
Patent number
US07985755B2

Reaction notes

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