Chloroacetaldehyde → Ammonium Hydroxide

HRID 1615858Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1615858
[F:1][C:2]1[CH:3]=[C:4]([C@@:9]2([CH3:41])[N:18]([CH2:19][C:20]#[C:21][C:22]3[CH:23]=[C:24]4[CH2:39][C@@:29]5([C:37]6[C:32](=[N:33][CH:34]=[CH:35][CH:36]=6)[NH:31][C:30]5=[O:38])[CH2:28][C:25]4=[N:26][CH:27]=3)[C:17](=[O:40])[C:12]3([CH2:16][CH2:15][CH2:14][CH2:13]3)[NH:11][CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1.C(O)(=O)C.[Cl:46][CH2:47][CH:48]=O.C([BH3-])#N.[Na+]>CO>[NH4+:11].[OH-:38].[Cl:46][CH2:47][CH2:48][N:11]1[CH2:10][C@:9]([C:4]2[CH:5]=[C:6]([F:8])[CH:7]=[C:2]([F:1])[CH:3]=2)([CH3:41])[N:18]([CH2:19][C:20]#[C:21][C:22]2[CH:23]=[C:24]3[CH2:39][C@@:29]4([C:37]5[C:32](=[N:33][CH:34]=[CH:35][CH:36]=5)[NH:31][C:30]4=[O:38])[CH2:28][C:25]3=[N:26][CH:27]=2)[C:17](=[O:40])[C:12]21[CH2:13][CH2:14][CH2:15][CH2:16]2

Komponenten

7

Edukt 4

HCID 33Chloroacetaldehyde2×HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydride2×HCID 44469663(6S)-3-{3-[(8R)-8-(3,5-difluorophenyl)-8-methyl-10-oxo-6,9-diazaspiro[4.5]dec-9-yl]prop-1-yn-1-yl}-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one

Produkt 2

HCID 14923Ammonium HydroxideHCID 66865111(6S)-3-{3-[(8R)-6-(2-Chloroethyl)-8-(3,5-difluorophenyl)-8-methyl-10-oxo-6,9-diazaspiro[4.5]dec-9-yl]prop-1-yn-1-yl}-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Versuchsvorschrift

A solution of (6S)-3-{3-[(8R)-8-(3,5-difluorophenyl)-8-methyl-10-oxo-6,9-diazaspiro[4.5]dec-9-yl]prop-1-yn-1-yl}-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (100 mg, 0.18 mmol, described in Example 39), acetic acid (0.041 mL, 0.72 mmol), and chloroacetaldehyde (0.47 mL, 3.6 mmol, 50 wt % in H2O) in MeOH (5 mL) was stirred for 5 min. Sodium cyanoborohydride (34 mg, 0.54 mmol) was added and stirring was continued for 42 h. Additional chloroacetaldehyde (0.47 mL, 3.6 mmol, 50 wt % in H2O) and sodium cyanoborohydride (34 mg, 0.54 mmol) was added at 24 h. The reaction was quenched with saturated aqueous NaHCO3 (10 mL) and extracted with CH2Cl2 (3×10 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified on silica gel, eluting with a gradient of CH2Cl2:MeOH:NH4OH—100:0:0 to 90:10:1, to yield the title compound. MS: m/z=616 (M+1).

Aufarbeitung

  1. customThe reaction was quenched with saturated aqueous NaHCO3 (10 mL)
  2. extractionextracted with CH2Cl2 (3×10 mL)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified on silica gel
  7. washeluting with a gradient of CH2Cl2

Quellen und Nachweise

ORD-Eintrag
ord-2c3d1cc1507e4197a0ee82efdbe08d70
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08765759B2

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