Lithium Hexamethyldisilazide → HCID 58466300, compound

HRID 335935Notes

Reaction equation

Cl[C:2]1[N:7]=[CH:6][C:5]2[O:8][C:9]3[C:14]([C@@:15]4([CH2:19][O:18][C:17]([NH2:20])=[N:16]4)[C:4]=2[CH:3]=1)=[CH:13][C:12]([C:21]1[C:22]([F:27])=[N:23][CH:24]=[CH:25][CH:26]=1)=[CH:11][CH:10]=3.CN(C1C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=CC=CC=1)C.Cl.[F:57][C:58]1([F:63])[CH2:62][CH2:61][NH:60][CH2:59]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1.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:57][C:58]1([F:63])[CH2:62][CH2:61][N:60]([C:2]2[N:7]=[CH:6][C:5]3[O:8][C:9]4[C:14]([C@@:15]5([CH2:19][O:18][C:17]([NH2:20])=[N:16]5)[C:4]=3[CH:3]=2)=[CH:13][C:12]([C:21]2[C:22]([F:27])=[N:23][CH:24]=[CH:25][CH:26]=2)=[CH:11][CH:10]=4)[CH2:59]1

Participants

Conditions

Temperature: 90 °C

Procedure

To a resealable tube charged with a mixture of (S)-3-chloro-7-(2-fluoropyridin-3-yl)-5′H-spiro[chromeno[2,3-c]pyridine-5,4′-oxazol]-2′-amine (0.25 g, 0.653 mmol), pd2(dba)3 (0.030 g, 0.033 mmol), 2-(dicyclohexylphosphino)-2′-(n,n-dimethylamino)biphenyl (0.039 g, 0.098 mmol), and 3,3-difluoropyrrolidine hydrochloride (0.281 g, 1.959 mmol) was added 1.0 M lithium bis(trimethylsilyl)amide (3.92 mL, 3.92 mmol) in THF and the resulting mixture was heated at 90° C. for 24 h. The mixture was concentrated and purified by reverse phase HPLC to afford (S)-3-(3,3-difluoropyrrolidin-1-yl)-7-(2-fluoropyridin-3-yl)-5′H-spiro[chromeno[2,3-c]pyridine-5,4′-oxazol]-2′-amine.

Workup

concentrationThe mixture was concentrated
custompurified by reverse phase HPLC

Sources & evidence

ORD record: ord-a1d350243e694d03b0c26453379691ee
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08883782B2

Reaction notes

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