Ammonia → HCID 178455832, compound

HRID 2364769Notes

Reaction equation

HRID 2364769 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.[CH2:18]([C@H:20]1[N:29]([CH:30]([CH3:32])[CH3:31])[C:28]2[N:27]=[C:26]([NH:33][C:34]3[CH:35]=[CH:36][C:37]([C:43](O)=[O:44])=[C:38]4[C:42]=3[O:41][CH2:40][CH2:39]4)[N:25]=[CH:24][C:23]=2[N:22]([CH3:46])[C:21]1=[O:47])[CH3:19].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>[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]([NH:17][C:43]([C:37]4[CH:36]=[CH:35][C:34]([NH:33][C:26]5[N:25]=[CH:24][C:23]6[N:22]([CH3:46])[C:21](=[O:47])[C@@H:20]([CH2:18][CH3:19])[N:29]([CH:30]([CH3:31])[CH3:32])[C:28]=6[N:27]=5)=[C:42]5[O:41][CH2:40][CH2:39][C:38]=45)=[O:44])[CH2:13][CH2:12]3)[CH2:7][CH2:6]2)[CH2:2][CH2:3]1

Participants

7

Reactant 5

HCID 222AmmoniaHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 681080517-[[(7R)-7-ethyl-8-isopropyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylic acidHCID 178511578HCID 178511578, compound

Product 1

HCID 178455832HCID 178455832, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(cis)-4-[4-(Cyclopropylmethyl)piperazin-1-yl]cyclohexanamine 12e (577 mg, 2.43 mmol), 7-[[(7R)-7-ethyl-8-isopropyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylic acid 22f (1 g, 2.43 mmol), O-(benzotriazol-1-yl)-N,N,N′,N′-tetra methyluronium tetrafluoroborate (780 mg, 2.43 mmol) and diisopropylethylamine (690 mg, 5.35 mmol) were dissolved in 40 mL of dichloromethane. The reaction mixture was stirred for 2 hours. The resulting solution was added with 50 mL of aqueous ammonia and extracted with dichloromethane (50 mL×3). The combined organic phase was washed with saturated brine (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 with elution system A to obtain the title compound N-[(cis)-4-[4-(cyclopropylmethyl)piperazin-1-yl]cyclohexyl]-7-[[(7R)-7-ethyl-8-isopropyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxamide 44 (576 mg, yield: 38.0%) as a white solid.

Workup

  1. extractionextracted with dichloromethane (50 mL×3)
  2. washThe combined organic phase was washed with saturated brine (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 with elution system

Sources & evidence

ORD record
ord-87b49be36cfe488e89e1ce5821e8bd37
Source dataset
uspto-grants-2014_04
Patent number
US08691822B2

Reaction notes

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