Dimethylformamide → HCID 59239453, compound

HRID 1698044Notes

Reaction equation

HRID 1698044 reaction equation
[C:1]([CH2:3][C@H:4]1[C:9]2[N:10]=[C:11]([C:21]3[CH:26]=[CH:25][C:24]([NH:27][C:28]([NH:30][CH2:31][CH3:32])=[O:29])=[CH:23][CH:22]=3)[N:12]=[C:13]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][C@@H:15]3[CH3:20])[C:8]=2[CH2:7][CH2:6][N:5]1[CH:33]([CH3:35])[CH3:34])#[N:2].C(CC1C2N=C(C3C=CC(NC(NCC)=O)=CC=3)N=C(N3CCOC[C@@H]3C)C=2CCN1)#N.CN(C)C=O.C(N(CC)C(C)C)(C)C.C(I)(C)C>>[C:1]([CH2:3][C@@H:4]1[C:9]2[N:10]=[C:11]([C:21]3[CH:26]=[CH:25][C:24]([NH:27][C:28]([NH:30][CH2:31][CH3:32])=[O:29])=[CH:23][CH:22]=3)[N:12]=[C:13]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][C@@H:15]3[CH3:20])[C:8]=2[CH2:7][CH2:6][N:5]1[CH:33]([CH3:34])[CH3:35])#[N:2]

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 6362Isopropyl iodide2×HCID 81531Diisopropylethylamine2×HCID 44815097HCID 44815097, compoundHCID 67175716HCID 67175716, compound

Product 1

HCID 59239453HCID 59239453, compound

Conditions

Temperature
50 °C

Procedure

and 1-(4-((S)-8-(cyanomethyl)-7-isopropyl-4-((S)-3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)-3-ethylurea (xu2): 1-(4-(8-(cyanomethyl)-4-((S)-3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)-3-ethylurea (0.0947 g, 0.217 mmol) in dry N,N-Dimethylformamide (1.600 mL, 20.66 mmol) was added N,N-Diisopropylethylamine (0.1200 mL, 0.6888 mmol) followed by Isopropyl iodide (0.0460 mL, 0.460 mmol). The reaction mixture was heated at 50° C. and stirred overnight. The reaction mixture was heated at 80° C. and stirred overnight. The reaction mixture was heated at 90° C. overnight. Added Isopropyl iodide (0.1150 mL, 1.150 mmol) and N,N-Diisopropylethylamine (0.1200 mL, 0.6889 mmol). The reaction mixture was heated at 120° C. and stirred for 4 days. The reaction mixture was concentrated and chromatographed through silica gel (40 g, 0-5% MeOH in dichloromethane), purified by HPLC, and the diastereomers were separated out by SFC. Diastereomer 1 LC/MS-m/z+478.3 (M+H)+; Diastereomer 2 LC/MS-m/z+478.2 (M+H)+.

Workup

  1. temperatureThe reaction mixture was heated at 80° C.
  2. stirringstirred overnight
  3. temperatureThe reaction mixture was heated at 90° C. overnight
  4. temperatureThe reaction mixture was heated at 120° C.
  5. stirringstirred for 4 days
  6. concentrationThe reaction mixture was concentrated
  7. customchromatographed through silica gel (40 g, 0-5% MeOH in dichloromethane)
  8. custompurified by HPLC
  9. customthe diastereomers were separated out by SFC

Sources & evidence

ORD record
ord-d51182e4f4874db9a91e742a95195589
Source dataset
uspto-grants-2012_04
Patent number
US08163763B2

Reaction notes

Loading…