Ammonia → HCID 178455830, compound

HRID 2364692Notes

Reaction equation

HRID 2364692 reaction equation
[CH:1]1([CH2:4][N:5]2[CH2:10][CH2:9][N:8]([C@@H:11]3[CH2:16][CH2:15][C@H:14]([NH2:17])[CH2:13][CH2:12]3)[CH2:7][CH2:6]2)[CH2:3][CH2:2]1.[CH:18]1([N:23]2[C:32]3[N:31]=[C:30]([NH:33][C:34]4[CH:35]=[CH:36][C:37]([C:43](O)=[O:44])=[C:38]5[C:42]=4[O:41][CH2:40][CH2:39]5)[N:29]=[CH:28][C:27]=3[N:26]([CH3:46])[C:25](=[O:47])[C@H:24]2[CH2:48][CH3:49])[CH2:22][CH2:21][CH2:20][CH2:19]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.N>ClCCl.O>[CH:18]1([N:23]2[C:32]3[N:31]=[C:30]([NH:33][C:34]4[CH:35]=[CH:36][C:37]([C:43]([NH:17][C@H:14]5[CH2:15][CH2:16][C@@H:11]([N:8]6[CH2:9][CH2:10][N:5]([CH2:4][CH:1]7[CH2:2][CH2:3]7)[CH2:6][CH2:7]6)[CH2:12][CH2:13]5)=[O:44])=[C:38]5[C:42]=4[O:41][CH2:40][CH2:39]5)[N:29]=[CH:28][C:27]=3[N:26]([CH3:46])[C:25](=[O:47])[C@H:24]2[CH2:48][CH3:49])[CH2:19][CH2:20][CH2:21][CH2:22]1

Participants

8

Reactant 5

HCID 222AmmoniaHCID 81531DiisopropylethylamineHCID 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 178511578HCID 178511578, compound

Product 1

HCID 178455830HCID 178455830, compoundYield 61%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

(cis)-4-[4-(Cyclopropylmethyl)piperazin-1-yl]cyclohexanamine 12e (139 mg, 0.40 mmol), 7-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylic acid 1q (175 mg, 0.40 mmol), O-(benzotriazol-1-yl)-N,N,N′,N′-tetra methyluronium tetrafluoroborate (128 mg, 0.40 mmol) and diisopropylethylamine (258 mg, 2.08 mmol) were dissolved in 50 mL of dichloromethane. The reaction solution was stirred for 2 hours followed by the addition of 50 mL of water and 10 mL of aqueous ammonia successively, and stirred for another 0.5 hours. The resulting solution was extracted with dichloromethane (50 mL×3). The combined organic phase was washed with saturated sodium chloride solution (50 mL×3), dried over anhydrous magnesium sulfate. 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-[(cis)-4-[4-(cyclopropylmethyl)piperazin-1-yl]cyclohexyl]-2,3-dihydrobenzofuran-4-carboxamide 12 (160 mg, yield: 61.0%) as a white solid.

Workup

  1. stirringstirred for another 0.5 hours
  2. extractionThe resulting solution was extracted with dichloromethane (50 mL×3)
  3. washThe combined organic phase was washed with saturated sodium chloride solution (50 mL×3)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-0bcba7eeffbe496eafe83aa1d3b989a6
Source dataset
uspto-grants-2014_04
Patent number
US08691822B2

Reaction notes

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