Isopropanol → Ammonia methanol

HRID 710210Notes

Reaction equation

[CH3:1][C:2]1([CH3:20])[CH2:7][CH:6]([NH:8][C:9]2[C:14]([C:15]#[N:16])=[CH:13][N:12]=[C:11](Cl)[N:10]=2)[CH2:5][C:4]([CH3:19])([CH3:18])[NH:3]1.[CH:21]1([C:24]2[C:29]([N:30]3[CH:34]=[N:33][N:32]=[N:31]3)=[CH:28][C:27]([NH2:35])=[CH:26][C:25]=2[F:36])[CH2:23][CH2:22]1.C[CH:38]([OH:40])C>>[NH3:3].[CH3:38][OH:40].[CH3:1][C:2]1([CH3:20])[CH2:7][CH:6]([NH:8][C:9]2[C:14]([C:15]#[N:16])=[CH:13][N:12]=[C:11]([NH:35][C:27]3[CH:28]=[C:29]([N:30]4[CH:34]=[N:33][N:32]=[N:31]4)[C:24]([CH:21]4[CH2:22][CH2:23]4)=[C:25]([F:36])[CH:26]=3)[N:10]=2)[CH2:5][C:4]([CH3:19])([CH3:18])[NH:3]1

Participants

Reactant 3

HCID 3776Isopropanol

HCID 58065777HCID 58065777, compound

HCID 86661498HCID 86661498, compound

Product 2

HCID 21705897Ammonia methanolYield 1%

HCID 56644516HCID 56644516, compound

Conditions

Temperature: 50 °C

Procedure

A mixture of 4-(2,2,6,6-tetramethylpiperidin-4-ylamino)-2-chloropyrimidine-5-carbonitrile (72 mg, 0.243 mmol, 1 equiv), 4-cyclopropyl-3-fluoro-5-(1H-tetrazol-1-yl)benzenamine (64 mg, 0.292 mmol, 1.2 equiv), and PTSA monohydrate (37 mg, 0.195 mmol, 0.8 equiv) in IPA (2.5 mL) were heated to 50° C. for 4 hours. After cooling to ambient temperature, the crude mixture was quenched with 2M NH3/MeOH followed by concentrating to dryness and repeating once. The crude product was purified by flash chromatography and eluted with DCM:2M NH3/MeOH=100:0 to 96:4 using 1% 2M NH3/MeOH increments to provide the desired product which was recrystallized with IPA/hexane to give desired compound (61 mg, 53%) as a solid.

Workup

temperatureAfter cooling to ambient temperature
customthe crude mixture was quenched with 2M NH3/MeOH
concentrationby concentrating to dryness
customThe crude product was purified by flash chromatography
washeluted with DCM

Sources & evidence

ORD record: ord-01f917f8b2614500ab614f3ce2f15b6f
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181222B2

Reaction notes

Loading…