Diisopropylethylamine → HCID 178455831, compound

HRID 2364739Notes

Reaction equation

HRID 2364739 reaction equation
[CH:1]1([N:6]2[C:15]3[N:14]=[C:13]([NH:16][C:17]4[CH:18]=[CH:19][C:20]([C:26]([OH:28])=O)=[C:21]5[C:25]=4[O:24][CH2:23][CH2:22]5)[N:12]=[CH:11][C:10]=3[N:9]([CH3:29])[C:8](=[O:30])[C@H:7]2[CH2:31][CH3:32])[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:33]1([CH2:36][N:37]2[CH2:42][CH2:41][N:40]([C@H:43]3[CH2:48][CH2:47][C@H:46]([NH2:49])[CH2:45][CH2:44]3)[CH2:39][CH2:38]2)[CH2:35][CH2:34]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>[CH:1]1([N:6]2[C:15]3[N:14]=[C:13]([NH:16][C:17]4[CH:18]=[CH:19][C:20]([C:26]([NH:49][C@H:46]5[CH2:45][CH2:44][C@H:43]([N:40]6[CH2:39][CH2:38][N:37]([CH2:36][CH:33]7[CH2:34][CH2:35]7)[CH2:42][CH2:41]6)[CH2:48][CH2:47]5)=[O:28])=[C:21]5[C:25]=4[O:24][CH2:23][CH2:22]5)[N:12]=[CH:11][C:10]=3[N:9]([CH3:29])[C:8](=[O:30])[C@H:7]2[CH2:31][CH3:32])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 681074757-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylic acidHCID 178511579HCID 178511579, compound

Product 1

HCID 178455831HCID 178455831, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

7-[[(7R)-8-Cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylic acid 1q (140 mg, 0.346 mmol), (trans)-4-[4-(cyclopropylmethyl)piperazin-1-yl]cyclohexanamine 16b (76 mg, 0.35 mmol), O-(benzotriazol-1-yl)-N,N,N′,N′-tetra methyluronium tetrafluoroborate (102 mg, 0.32 mmol) and diisopropylethylamine (103 mg, 0.80 mmol) were dissolved in 25 mL of dichloromethane. The reaction solution was stirred for 2 hours. The resulting solution was added dropwise with saturated sodium bicarbonate solution to adjust pH to 8 to 9 and extracted with dichloromethane (50 mL×3). The combined organic phase was washed with water (20 mL) and saturated sodium chloride solution (20 mL) successively, 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 7-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-[(trans)-4-[4-(cyclopropylmethyl)piperazin-1-yl]cyclohexyl]-2,3-dihydrobenzofuran-4-carboxamide 34 (50 mg, yield: 40.0%) as a white solid.

Workup

  1. extractionextracted with dichloromethane (50 mL×3)
  2. washThe combined organic phase was washed with water (20 mL) and saturated sodium chloride solution (20 mL) successively
  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-f04dd7a3d04248048005bdf641380637
Source dataset
uspto-grants-2014_04
Patent number
US08691822B2

Reaction notes

Loading…