Ethylamine → HCID 178465182, compound

HRID 571415Notes

Reaction equation

HRID 571415 reaction equation
[CH3:1][O:2][CH2:3][C@@H:4]([NH:11][C:12](=[O:48])[NH:13][C:14]1[N:19]=[CH:18][C:17]2[C:20]([C@@H:42]3[CH2:44][C@H:43]3[C:45](O)=[O:46])=[N:21][N:22](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[C:16]=2[CH:15]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O.[CH3:67][CH2:68][N:69](C(C)C)C(C)C.C(N)C.C(O)(C(F)(F)F)=O.C([SiH](CC)CC)C>C(Cl)Cl>[CH2:68]([NH:69][C:45]([C@@H:43]1[CH2:44][C@H:42]1[C:20]1[C:17]2[CH:18]=[N:19][C:14]([NH:13][C:12]([NH:11][C@@H:4]([C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=3)[CH2:3][O:2][CH3:1])=[O:48])=[CH:15][C:16]=2[NH:22][N:21]=1)=[O:46])[CH3:67]

Participants

8

Reactant 6

HCID 6341EthylamineHCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 89525877trans-2-(6-(3-((S)-2-methoxy-1-phenylethyl)ureido)-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-yl)cyclopropanecarboxylic acid

Product 1

HCID 178465182HCID 178465182, compoundYield 53.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of trans-2-(6-(3-((S)-2-methoxy-1-phenylethyl)ureido)-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-yl)cyclopropanecarboxylic acid (13 mg, 0.020 mmol), 1-propanephosphonic acid cyclic anhydride (50% in EtOAc, 18.20 μl, 0.031 mmol), DIEA (10.68 μl, 0.061 mmol) and ethylamine (2M in THF) (102 μl, 0.204 mmol) in DCM (0.5 ml) was stirred at room temperature overnight and then concentrated. The residue was treated with TFA (500 μl, 6.49 mmol) and triethylsilane (7 μl, 0.044 mmol). The mixture was stirred at room temperature for 6 h and then concentrated. The residue was purified by preparative HPLC (Reverse phase C-18, Waters SunFire PrepODB, 150×19 mm, 5u), eluting with 10-90% Acetonitrile/Water+0.1% TFA (20 mL/min) over 15 min. to give trans-N-ethyl-2-(6-(3-((S)-2-methoxy-1-phenylethyl)ureido)-1H-pyrazolo[4,3-c]pyridin-3-yl)cyclopropanecarboxamide (4.5 mg, 52% yield). MS ESI calc'd. for C22H26N6O3[M+1]+ 423, found 423. MS ESI calc'd. for C22H26N6O3[M−1]− 421, found 421.

Workup

  1. concentrationconcentrated
  2. stirringThe mixture was stirred at room temperature for 6 h
  3. concentrationconcentrated
  4. customThe residue was purified by preparative HPLC (Reverse phase C-18, Waters SunFire PrepODB, 150×19 mm, 5u)
  5. washeluting with 10-90% Acetonitrile/Water+0.1% TFA (20 mL/min) over 15 min.

Sources & evidence

ORD record
ord-f130e765b1414437ae14a2d002676307
Source dataset
uspto-grants-2015_05
Patent number
US09023865B2

Reaction notes

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