Tris(hydroxymethyl)aminomethane → HCID 25002761, compound

HRID 1015349Notes

Reaction equation

HRID 1015349 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([CH2:7][O:8][C:9]2[CH:18]=[CH:17][CH:16]=[C:15]3[C:10]=2[C:11]([NH2:20])=[N:12][C:13]([NH2:19])=[N:14]3)[CH2:3][CH2:2]1.CN1CCOCC1.[F:28][C:29]1[CH:30]=[C:31]([CH:35]=[CH:36][C:37]=1[F:38])[C:32](Cl)=[O:33].C(O)C(N)(CO)CO>CN(C)C=O>[NH2:19][C:13]1[N:12]=[C:11]([NH2:20])[C:10]2[C:15](=[CH:16][CH:17]=[CH:18][C:9]=2[O:8][CH2:7][CH:4]2[CH2:5][CH2:6][N:1]([C:32]([C:31]3[CH:35]=[CH:36][C:37]([F:38])=[C:29]([F:28])[CH:30]=3)=[O:33])[CH2:2][CH2:3]2)[N:14]=1

Participants

6

Reactant 4

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 79724-MethylmorpholineHCID 27245193,4-Difluorobenzoyl chlorideHCID 575765655-(Piperidin-4-ylmethoxy)quinazoline-2,4-diamine

Product 1

HCID 25002761HCID 25002761, compoundYield 157.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-(Piperidin-4-ylmethoxy)quinazoline-2,4-diamine (50 mg; 0.18 mmol) was shaken for 60 hours at room temperature in the presence of 3-(morpholino)propyl polystyrene sulfonamide (PS-NMM) (160 mg; 0.4 mmol) and 3,4-difluorobenzoyl chloride (65.3 mg; 0.37 mmol) in 4 mL N,N-dimethylformamide. Tris-(2-aminoethyl)aminomethyl polystyrene (PS-Trisamine) (112 mg; 0.4 mmol) was then added to the mixture and continued to shake for an additional 2 hours. Resins were filtered off and rinsed with methanol. Filtrate was concentrated at reduced pressure, and residue was triturated with 2 mL 1 N NaOH and ethanol (1:1). Solids were collected by filtration to yield [4-(2,4-diamino-quinazolin-5-yloxymethyl)-piperidin-1-yl]-(3,4-difluorophenyl)-methanone (117.4 mg; 76% yield). 1HNMR (400 MHz, DMSO-d6) δ 7.51 (m, 2H), 7.35 (t, J=8.4 Hz, 1H), 7.26 (m, 3H), 6.77 (d, J=8.4 Hz, 1H), 6.54 (d, J=8.4 Hz, 1H), 5.94 (br s, 2H), 4.50 (br s, 1H), 4.03 (d, J=6.0 Hz, 2H), 3.60 (br s, 1H), 3.11 (br s, 1H), 2.82 (br s, 1H), 2.22 (s, 1H), 1.87 (br s, 1H), 1.75 (br s, 1H), 1.31 (m, 2H). MS m/z (ESI) 414 (M+H)+.

Workup

  1. filtrationResins were filtered off
  2. washrinsed with methanol
  3. concentrationFiltrate was concentrated at reduced pressure, and residue
  4. customwas triturated with 2 mL 1 N NaOH and ethanol (1:1)
  5. filtrationSolids were collected by filtration

Sources & evidence

ORD record
ord-8d587240d94b454fb00279fa22a66964
Source dataset
uspto-grants-2011_07
Patent number
US07985755B2

Reaction notes

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