Hydrochloric Acid → HCID 68463421, compound

HRID 506177Notes

Reaction equation

HRID 506177 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[N:10][CH:11]=[C:12]([C:15]=2[NH:16][C:17]2[CH:25]=[CH:24][CH:23]=[C:22]3[C:18]=2[CH:19]=[CH:20][NH:21]3)[C:13]#[N:14])=[CH:4][CH:3]=1.[CH2:26]([C@H:33]([NH:36]C(=O)OC(C)(C)C)[CH2:34]O)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.N(C(OCC)=O)=NC(OCC)=O.Cl>C1COCC1>[NH2:36][C@@H:33]([CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH2:34][O:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:9]=[N:10][CH:11]=[C:12]([C:15]=2[NH:16][C:17]2[CH:25]=[CH:24][CH:23]=[C:22]3[C:18]=2[CH:19]=[CH:20][NH:21]3)[C:13]#[N:14])=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 2733675tert-butyl N-[(2S)-1-hydroxy-3-phenylpropan-2-yl]carbamateHCID 68463685HCID 68463685, compound

Product 1

HCID 68463421HCID 68463421, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 5-(4-hydroxyphenyl)-4-(1H-indol-4-ylamino)nicotinonitrile 225 (100 mg, 0.31 mmol), tert-butyl (1S)-1-benzyl-2-hydroxyethylcarbamate (77 mg, 0.31 mmol), and Ph3P (97 mg, 0.37 mmol) in THF (2.0 mL) was added diethyl azodicarboxylate (64 mg, 0.37 mmol) via a syringe over 6 min. The resulting mixture was stirred at r.t. for 21 h and treated with concentrated HCl (˜200 mg). After heating at 60° C. for one h, the reaction mixture was partitioned between saturated NaHCO3 and CH2Cl2. The combined organics were dried over Na2SO4, concentrated and purified by silica gel flash column chromatography (eluting with 4% MeOH/CH2Cl2) to give 42 mg (30%) of 5-(4-{[(2S)-2-amino-3-phenylpropyl]oxy}phenyl)-4-(1H-indol-4-ylamino)nicotinonitrile 226 as a white solid. MS: 460.4 (M+H); melting range: 83-85° C.

Workup

  1. temperatureAfter heating at 60° C. for one h
  2. customthe reaction mixture was partitioned between saturated NaHCO3 and CH2Cl2
  3. dry with materialThe combined organics were dried over Na2SO4
  4. concentrationconcentrated
  5. custompurified by silica gel flash column chromatography (eluting with 4% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-fb06c6b68cda42dc894c453977d34041
Source dataset
uspto-grants-2010_08
Patent number
US07781591B2

Reaction notes

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