Acetonitrile → HCID 86719408, compound

HRID 510360Notes

Reaction equation

HRID 510360 reaction equation
[NH2:1][C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:13][CH:12]=3)=[C:9]([N+:24]([O-])=O)[N:8]([C@@H:27]3[CH2:31][CH2:30][N:29]([C:32](=[O:41])/[CH:33]=[CH:34]/[CH2:35][N:36]([CH:38]4[CH2:40][CH2:39]4)[CH3:37])[CH2:28]3)[C:4]=2[N:5]=[CH:6][N:7]=1.[NH4+].[Cl-].C(#N)C>C1COCC1.CO.O.O.[Fe]>[CH:38]1([N:36]([CH3:37])[CH2:35]/[CH:34]=[CH:33]/[C:32]([N:29]2[CH2:30][CH2:31][C@@H:27]([N:8]3[C:4]4[N:5]=[CH:6][N:7]=[C:2]([NH2:1])[C:3]=4[C:10]([C:11]4[CH:12]=[CH:13][C:14]([O:17][C:18]5[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=5)=[CH:15][CH:16]=4)=[C:9]3[NH2:24])[CH2:28]2)=[O:41])[CH2:40][CH2:39]1

Participants

7

Reactant 3

HCID 6342AcetonitrileHCID 25517Ammonium ChlorideHCID 86719409HCID 86719409, compound

Product 1

HCID 86719408HCID 86719408, compoundYield 6%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 962WaterSolventHCID 21892291Methanol tetrahydrofuran waterSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred solution of (R,E)-1-(3-(4-amino-6-nitro-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidin-1-yl)-4-(cyclopropyl(methyl)amino)but-2-en-1-one (160) (227 mg, 0.41 mmol) in THF/MeOH/H2O (4 mL/2 mL/1 mL) was added iron powder (92 mg, 1.64 mmol) and NH4Cl (89 mg, 1.64 mmol). The resulting mixture was heated at 50° C. for 1 hrs under N2, and then filtered through a pad of Celite. The filtrate was directly loaded and purified by preparative HPLC (RP, C18, 10 to 95% acetonitrile in water (0.1% HCOOH)) to give (R,E)-4-(cyclopropyl(methyl)amino)-1-(3-(4,6-diamino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidin-1-yl)but-2-en-1-one (162) (12 mg, 6% yield) as a white solid. LC-MS (ESI): m/z (M+1) 524.1. 1H NMR (400 MHz, DMSO) δ 8.21 (s, 1H), 7.91 (d, J=6.4 Hz, 1H), 7.40 (t, J=7.8 Hz, 2H), 7.32 (d, J=5.6 Hz, 2H), 7.14 (t, J=7.2 Hz, 1H), 7.07 (t, J=6.9 Hz, 3H), 6.74-6.57 (m, 1H), 6.38 (dd, J=31.6, 15.5 Hz, 1H), 5.51 (s, 2H), 5.25 (d, J=11.5 Hz, 2H), 5.17-4.96 (m, 1H), 4.35-3.45 (m, 4H), 3.29-3.20 (m, 3H), 3.09-2.94 (m, 1H), 2.22 (d, J=15.3 Hz, 3H), 1.76-1.61 (m, 1H), 0.47-0.34 (m, 2H), 0.34-0.22 (m, 2H).

Workup

  1. filtrationfiltered through a pad of Celite
  2. custompurified by preparative HPLC (RP

Sources & evidence

ORD record
ord-be7b86498c3945c19b4b6da55cdacdb1
Source dataset
uspto-grants-2015_08
Patent number
US09096604B2

Reaction notes

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