Pyridine → HCID 71543161, compound

HRID 931656Notes

Reaction equation

HRID 931656 reaction equation
[CH3:1][O:2][C:3]1[N:4]=[CH:5][C:6]([C:9]([OH:11])=O)=[N:7][CH:8]=1.N1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.CN(C([O:25]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:42][C:43]1[S:44][CH2:45][CH2:46][C@@:47]2([N:64]=1)[C:60]1[CH:59]=[C:58](O)[CH:57]=[C:56]([F:62])[C:55]=1[O:54][C:53]1[C:48]2=[CH:49][C:50]([NH2:63])=[CH:51][CH:52]=1>CN(C=O)C>[NH2:42][C:43]1[S:44][CH2:45][CH2:46][C@:47]2([N:64]=1)[C:48]1[CH:49]=[C:50]([NH:63][C:9]([C:6]3[CH:5]=[N:4][C:3]([O:2][CH3:1])=[CH:8][N:7]=3)=[O:11])[CH:51]=[CH:52][C:53]=1[O:54][C:55]1[C:60]2=[CH:59][C:58]([C:15]2[CH2:14][CH2:13][O:25][CH2:17][CH:16]=2)=[CH:57][C:56]=1[F:62]

Participants

6

Reactant 4

HCID 1049PyridineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 457898115-Methoxy-2-pyrazinecarboxylic acidHCID 117600290HCID 117600290, compound

Product 1

HCID 71543161HCID 71543161, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

5-Methoxypyrazine-2-carboxylic acid (0.438 g, 2.84 mmol) was dissolved in DMF (15.09 ml). Pyridine, anhydrous (0.492 ml, 6.04 mmol) was added followed by HATU (1.492 g, 3.92 mmol), and the mixture was stirred for 30 minutes, then cooled to 0° C., and (S)-2,7′-diamino-4′-fluoro-5,6-dihydrospiro[[1,3]thiazine-4,9′-xanthen]-2′-ol (1.0 g, 3.02 mmol) was added. The solution was stirred at 0° C. for 45 min, then allowed to warm to RT and stirred for additional 2 hrs. At this point, LCMS (117271-22-1) indicated complete conversion to the desired product with MS+=468 (M+1). No bis-amide was detected. Water was added to quench the reaction. The resulted suspension was stirred for 25 min, then filtered. The filter cake was rinsed with water a few times, and then dried in air affording (S)—N-(2-amino-4′-fluoro-2′-hydroxy-5,6-dihydrospiro[[1,3]thiazine-4,9′-xanthen]-7′-yl)-5-methoxypyrazine-2-carboxamide (1.2 g, 2.57 mmol, 85% yield) as red solid. MS m/z=468.0 [M+H]. This intermediate was carried on without purification.

Workup

  1. stirringThe solution was stirred at 0° C. for 45 min
  2. temperatureto warm to RT
  3. stirringstirred for additional 2 hrs

Sources & evidence

ORD record
ord-3cd5741dd444434598eb215a7ae125d7
Source dataset
uspto-grants-2016_03
Patent number
US09296759B2

Reaction notes

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