Diisopropylethylamine → N-[(4-benzylmorpholin-2-yl)methyl]-7-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxamide

HRID 2364672Notes

Reaction equation

HRID 2364672 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([CH2:14][NH2:15])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:16]1([N:21]2[C:30]3[N:29]=[C:28]([NH:31][C:32]4[CH:33]=[CH:34][C:35]([C:41](O)=[O:42])=[C:36]5[C:40]=4[O:39][CH2:38][CH2:37]5)[N:27]=[CH:26][C:25]=3[N:24]([CH3:44])[C:23](=[O:45])[C@H:22]2[CH2:46][CH3:47])[CH2:20][CH2:19][CH2:18][CH2:17]1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.C(=O)(O)[O-].[Na+]>ClCCl>[CH2:1]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([CH2:14][NH:15][C:41]([C:35]2[CH:34]=[CH:33][C:32]([NH:31][C:28]3[N:27]=[CH:26][C:25]4[N:24]([CH3:44])[C:23](=[O:45])[C@@H:22]([CH2:46][CH3:47])[N:21]([CH:16]5[CH2:17][CH2:18][CH2:19][CH2:20]5)[C:30]=4[N:29]=3)=[C:40]3[O:39][CH2:38][CH2:37][C:36]=23)=[O:42])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 2776360(4-Benzylmorpholin-2-yl)methanamineHCID 681074757-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylic acid

Product 1

HCID 68107811N-[(4-benzylmorpholin-2-yl)methyl]-7-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxamideYield 44%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The crude compound (4-benzylmorpholin-2-yl)methanamine 2d (141 mg, 0.69 mmol), 7-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylic acid 1q (300 mg, 0.69 mmol), O-(benzotriazol-1-yl)-N,N,N′,N′-tetra methyluronium tetrafluoroborate (221 mg, 0.69 mmol) and diisopropylethylamine (260 mL, 1.52 mmol) were dissolved in 40 mL of dichloromethane, stirred for 12 hours. The resulting mixture was added with 50 mL of saturated sodium bicarbonate solution, extracted with dichloromethane (50 mL×3). The combined organic phase was washed with saturated sodium chloride solution (50 mL×3), then dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound N-[(4-benzylmorpholin-2-yl)methyl]-7-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxamide 2e (190 mg, yield: 44.0%) as a white solid.

Workup

  1. extractionextracted with dichloromethane (50 mL×3)
  2. washThe combined organic phase was washed with saturated sodium chloride solution (50 mL×3)
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-b4a0526043f849478d13f24c7fb43fad
Source dataset
uspto-grants-2014_04
Patent number
US08691822B2

Reaction notes

Loading…