Diisopropylethylamine → HCID 66865455, compound

HRID 1615861Notes

Reaction equation

HRID 1615861 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@@:9]2([CH3:42])[N:18]([CH2:19][C:20](=O)[O:21]C3C(F)=C(F)C(F)=C(F)C=3F)[C:17](=[O:34])[C:12]3([CH2:16][CH2:15][CH2:14][CH2:13]3)[N:11]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1.[OH:43][C:44]1[CH:45]=[C:46]2[C:67](=[CH:68][CH:69]=1)[CH2:66][C@:48]1([C:56]3[C:51](=[N:52][CH:53]=[CH:54][CH:55]=3)[N:50]([CH2:57][O:58][CH2:59][CH2:60][Si:61]([CH3:64])([CH3:63])[CH3:62])[C:49]1=[O:65])[CH2:47]2.C(N(CC)C(C)C)(C)C>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([C@@:9]2([CH3:42])[N:18]([CH2:19][C:20](=[O:21])[O:43][C:44]3[CH:45]=[C:46]4[C:67](=[CH:68][CH:69]=3)[CH2:66][C@:48]3([C:56]5[C:51](=[N:52][CH:53]=[CH:54][CH:55]=5)[N:50]([CH2:57][O:58][CH2:59][CH2:60][Si:61]([CH3:62])([CH3:63])[CH3:64])[C:49]3=[O:65])[CH2:47]4)[C:17](=[O:34])[C:12]3([CH2:16][CH2:15][CH2:14][CH2:13]3)[N:11]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 58118678HCID 58118678, compound2×HCID 86650290HCID 86650290, compound

Product 1

HCID 66865455HCID 66865455, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of tert-butyl (8R)-8-(3,5-difluorophenyl)-8-methyl-10-oxo-9-[2-oxo-2-(pentafluorophenoxy)ethyl]-6,9-diazaspiro[4.5]decane-6-carboxylate from Step A (119 mg, 0.197 mmol), (2R)-5-hydroxy-1′-{[2-(trimethylsilyl)ethoxy]methyl}-1,3-dihydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (77 mg, 0.201 mmol, described in Intermediate 35), and N,N-diisopropylethylamine (0.17 mL, 0.98 mmol) in DMF (0.5 mL) was heated at 150° C. in a microwave reactor for 30 min. The reaction mixture was cooled and partitioned between saturated aqueous NaHCO3 (20 mL) and EtOAc (30 mL). The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified on silica gel, eluting with a gradient of hexanes:EtOAc—100:0 to 0:100, to provide the title compound. MS: m/z=803.7 (M+1).

Workup

  1. temperatureThe reaction mixture was cooled
  2. custompartitioned between saturated aqueous NaHCO3 (20 mL) and EtOAc (30 mL)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified on silica gel
  7. washeluting with a gradient of hexanes

Sources & evidence

ORD record
ord-8b8913e8cb8f4bdcb4ae5dbd3d0aa477
Source dataset
uspto-grants-2014_07
Patent number
US08765759B2

Reaction notes

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