Bicarbonate Ion → HCID 71542133, compound

HRID 931635Notes

Reaction equation

HRID 931635 reaction equation
[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1.[Cl:19][C:20]1[CH:21]=[CH:22][C:23]([C:26]([OH:28])=O)=[N:24][CH:25]=1.[Br:29][C:30]1[CH:31]=[C:32]2[C@:43]3([CH2:48][CH2:47][O:46][C:45]([NH2:49])=[N:44]3)[C:42]3[C:37](=[CH:38][CH:39]=[C:40]([NH2:50])[CH:41]=3)[O:36][C:33]2=[N:34][CH:35]=1.C(=O)(O)[O-]>CO.C1COCC1.CCOC(C)=O.O>[NH2:49][C:45]1[O:46][CH2:47][CH2:48][C@:43]2([C:32]3[C:33](=[N:34][CH:35]=[C:30]([Br:29])[CH:31]=3)[O:36][C:37]3[C:42]2=[CH:41][C:40]([NH:50][C:26](=[O:28])[C:23]2[CH:22]=[CH:21][C:20]([Cl:19])=[CH:25][N:24]=2)=[CH:39][CH:38]=3)[N:44]=1

Participants

9

Reactant 4

HCID 769Bicarbonate IonHCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chlorideHCID 27628725-Chloro-2-picolinic acidHCID 89473219HCID 89473219, compound

Product 1

HCID 71542133HCID 71542133, compoundYield 20.6%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (228 mg, 0.775 mmol) was added to a solution of 5-chloro-2-pyridinecarboxylic acid (122 mg, 0.775 mmol) in MeOH (0.6 mL), followed by a solution of (S)-3-bromo-5′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,4′-[1,3]oxazine]-2′,7-diamine (140 mg, 0.388 mmol) in THF (1.6 mL) MeOH (0.5 mL). The reaction mixture was allowed to stir for 20 min at rt. Diluted, aqueous bicarbonate solution was added, followed by additional water and EtOAc. The organic phase was separated and dried over MgSO4. The solvent was removed under reduced pressure and the residue was purified by flash chromatography (silica gel, 20-100% EtOAc/hexanes). 40 mg of (S)—N-(2′-amino-3-bromo-5′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,4′-[1,3]oxazin]-7-yl)-5-chloropicolinamide were obtained as an off-white solid. MS m/z=501.7 [M+H]11. Calculated for C21H15BrClN5O3: 500.73. 1H NMR (300 MHz, CHLOROFORM-d) ppm 1.82-1.93 (m, 1H) 1.93-2.02 (m, 1H) 4.07-4.19 (m, 1H) 4.19-4.32 (m, 1H) 7.31 (d, J=8.62 Hz, 1H) 7.71 (d, J=2.48 Hz, 1H) 7.73-7.79 (m, 1H) 7.89 (dd, J=8.33, 2.34 Hz, 1H) 7.93 (d, J=2.48 Hz, 1H) 8.26 (d, J=8.33 Hz, 1H) 8.31 (d, J=2.48 Hz, 1H) 8.58 (d, J=1.90 Hz, 1H) 9.86 (s, 1H).

Workup

  1. additionDiluted
  2. customThe organic phase was separated
  3. dry with materialdried over MgSO4
  4. customThe solvent was removed under reduced pressure
  5. customthe residue was purified by flash chromatography (silica gel, 20-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-4b7ec6f3050b428daafd7c32126a7299
Source dataset
uspto-grants-2016_03
Patent number
US09296759B2

Reaction notes

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