Potassium Carbonate → (R)-tert-Butyl 4-fluoro-2-(4-(8-fluorochroman-4-ylamino)-5-nitropyrimidin-2-ylamino)phenylcarbamate

HRID 1363170Notes

Reaction equation

HRID 1363170 reaction equation
Cl.[F:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:12]=1[O:11][CH2:10][CH2:9][C@H:8]2[NH2:13].C(=O)([O-])[O-].[K+].[K+].[F:20][C:21]1[CH:26]=[CH:25][C:24]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[C:23]([NH:35][C:36]2[N:41]=[C:40](SC#N)[C:39]([N+:45]([O-:47])=[O:46])=[CH:38][N:37]=2)[CH:22]=1>CS(C)=O.C(#N)C>[F:20][C:21]1[CH:26]=[CH:25][C:24]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[C:23]([NH:35][C:36]2[N:37]=[C:38]([NH:13][C@H:8]3[C:7]4[C:12](=[C:3]([F:2])[CH:4]=[CH:5][CH:6]=4)[O:11][CH2:10][CH2:9]3)[C:39]([N+:45]([O-:47])=[O:46])=[CH:40][N:41]=2)[CH:22]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 52911303(R)-8-fluorochroman-4-amine hydrochlorideHCID 59704889tert-Butyl 4-fluoro-2-(5-nitro-4-thiocyanatopyrimidin-2-ylamino)phenylcarbamate

Product 1

HCID 66970500(R)-tert-Butyl 4-fluoro-2-(4-(8-fluorochroman-4-ylamino)-5-nitropyrimidin-2-ylamino)phenylcarbamateYield 83%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6342AcetonitrileSolvent

Procedure

A solution of the (R)-8-fluorochroman-4-amine hydrochloride (104 mg) in DMSO (2 mL) and potassium carbonate (141 mg) were added to a stirred solution of tert-butyl 4-fluoro-2-(5-nitro-4-thiocyanatopyrimidin-2-ylamino)phenylcarbamate (140 mg) in ACN (10 mL). The mixture was stirred for 15 hr at room temperature then partitioned between brine and EtOAc and separated. The aq. layer was washed with additional EtOAc, the combined organics were evaporated and purified via column chromatography, elution with 20-30% EtOAc/H gave the titled product in 83% yield. 1H-NMR (300 MHz, CDCl3) δ 9.1 (s, 1H), 8.7 (m, 1H), 8.2 (br s, 1H), 7.7 (m, 1H), 7.3 (m, 1H), 7.3-6.8 (m, 4H), 6.5 (s, 1H), 5.5 (br s, 1H), 4.4 (m 2H), 2.4 (m, 1H), 2.2 (m, 1H), 1.5 (s, 9H); MH+=515, 459 (-tBu).

Workup

  1. customthen partitioned between brine and EtOAc
  2. customseparated
  3. washThe aq. layer was washed with additional EtOAc
  4. customthe combined organics were evaporated
  5. custompurified via column chromatography, elution with 20-30% EtOAc/H

Sources & evidence

ORD record
ord-f6607f7f376146b69f700cdc31060f6f
Source dataset
uspto-grants-2011_02
Patent number
US07884109B2

Reaction notes

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