Ammonia → HCID 67071262, compound

HRID 388572Notes

Reaction equation

HRID 388572 reaction equation
C[O:2][C:3]([C@@H:5]1[CH2:9][C@H:8]([N:10]2[CH2:18][C:17]3[C:12](=[CH:13][C:14]([NH:23][C:24]4[N:29]=[C:28]([NH:30][C:31]5[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=5[S:37]([CH:40]([CH3:42])[CH3:41])(=[O:39])=[O:38])[C:27]([Cl:43])=[CH:26][N:25]=4)=[C:15]([O:19][CH:20]([CH3:22])[CH3:21])[CH:16]=3)[C:11]2=[O:44])[CH2:7][NH:6]1)=O.CO.[NH3:47]>>[Cl:43][C:27]1[C:28]([NH:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=2[S:37]([CH:40]([CH3:41])[CH3:42])(=[O:39])=[O:38])=[N:29][C:24]([NH:23][C:14]2[CH:13]=[C:12]3[C:17]([CH2:18][N:10]([C@@H:8]4[CH2:7][NH:6][C@H:5]([C:3]([NH2:47])=[O:2])[CH2:9]4)[C:11]3=[O:44])=[CH:16][C:15]=2[O:19][CH:20]([CH3:21])[CH3:22])=[N:25][CH:26]=1

Participants

4

Reactant 3

HCID 222AmmoniaHCID 887MethanolHCID 59764591HCID 59764591, compound

Product 1

HCID 67071262HCID 67071262, compound

Procedure

(2S,4S)-4-(6-{5-Chloro-4-[2-(propane-2-sulfonyl)-phenylamino]-pyrimidin-2-ylamino}-5-isopropoxy-1-oxo-1,3-dihydro-isoindol-2-yl)-pyrrolidine-2-carboxylic acid methyl ester generated in Step 1 (20 mg, 0.03 mmol) is dissolved in 7 N ammonia solution in MeOH (3 mL, 21 mmol). The resulting solution is heated using microwave irradiation to 120° C. for 1 h. After cooling to room temperature, the reaction mixture is concentrated in vacuo, neutralized to pH=8 with saturated aqueous NaHCO3, and extracted with DCM. The organic extracts are dried over Na2SO4, filtered, and concentrated in vacuo to give (2S,4S)-4-(6-{5-Chloro-4-[2-(propane-2-sulfonyl)-phenylamino]-pyrimidin-2-ylamino}-5-isopropoxy-1-oxo-1,3-dihydro-isoindol-2-yl)-pyrrolidine-2-carboxylic acid amide (177) as a yellow solid. 1H NMR 400 MHz (DMSO-d6 with trace D2O) δ 8.47(d, 1H), 8.25 (s, 1H), 8.07 (s, 1H), 7.78 (dd, 1H), 7.68 (m, 1H), 7.31(t, 1H), 7.24 (s, 1H), 4.71 (m, 2H), 4.43 (dd, 2H), 3.60 (m, 1H), 3.44 (m, 1H), 3.35 (m, 1H), 2.63 (m, 1H), 2.28 (m, 1H), 1.22 (d, 6H), 1.10 (d, 6H); MS m/z 628 (M+1).

Workup

  1. temperatureThe resulting solution is heated
  2. custommicrowave irradiation to 120° C. for 1 h
  3. concentrationthe reaction mixture is concentrated in vacuo
  4. extractionextracted with DCM
  5. dry with materialThe organic extracts are dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-943c2edda4d7439e950964f1f9f13372
Source dataset
uspto-grants-2013_02
Patent number
US08377921B2

Reaction notes

Loading…