Lithium Hexamethyldisilazide → (5S)-3-(3,3-difluoro-1-pyrrolidinyl)-7-((3-methyl-3-oxetanyl)ethynyl)spiro[chromeno[2,3-c]pyridine-5,4'-[1,3]oxazol]-2'-amine

HRID 335837Notes

Reaction equation

CN(C1C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=CC=CC=1)C.Cl.[F:30][C:31]1([F:36])[CH2:35][CH2:34][NH:33][CH2:32]1.Cl[C:38]1[N:43]=[CH:42][C:41]2[O:44][C:45]3[C:50]([C@@:51]4([CH2:55][O:54][C:53]([NH2:56])=[N:52]4)[C:40]=2[CH:39]=1)=[CH:49][C:48]([C:57]#[C:58][C:59]1([CH3:63])[CH2:62][O:61][CH2:60]1)=[CH:47][CH:46]=3.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:30][C:31]1([F:36])[CH2:35][CH2:34][N:33]([C:38]2[N:43]=[CH:42][C:41]3[O:44][C:45]4[C:50]([C@@:51]5([CH2:55][O:54][C:53]([NH2:56])=[N:52]5)[C:40]=3[CH:39]=2)=[CH:49][C:48]([C:57]#[C:58][C:59]2([CH3:63])[CH2:60][O:61][CH2:62]2)=[CH:47][CH:46]=4)[CH2:32]1

Participants

Conditions

Temperature: 90 °C

Procedure

Tris(dibenzylideneacetone)dipalladium (0) (0.012 g, 0.013 mmol), 2-(dicyclohexylphosphino)-2′-(n,n-dimethylamino)biphenyl (0.015 g, 0.039 mmol), 3,3-difluoropyrolidine HCl, 98% (0.113 g, 0.786 mmol) and (S)-3-chloro-7-((3-methyloxetan-3-yl)ethynyl)-5′H-spiro[chromeno[2,3-c]pyridine-5,4′-oxazol]-2′-amine (0.100 g, 0.262 mmol) were combined and degassed with nitrogen. LHMDS (1.06 m solution in THF) (1.571 mL, 1.571 mmol) was added and the mixture was stirred at 90° C. overnight. The solvent was removed and the crude material was purified by column chromatography with 0-5% 2M NH3 in MeOH/CH2Cl2 to provide the desired product as an off white solid. MS m/z=452.9 [M+H].

Workup

customdegassed with nitrogen
customThe solvent was removed
customthe crude material was purified by column chromatography with 0-5% 2M NH3 in MeOH/CH2Cl2

Sources & evidence

ORD record: ord-09664096d0ac4ea1a6f32c33c03a06e0
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08883782B2

Reaction notes

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