Dichloromethane → N-((R)-1-(4-chloro-3-fluorophenyl)propyl)-2-((S)-1-hydroxybutan-2-ylamino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxamide

HRID 2279508Notes

Reaction equation

HRID 2279508 reaction equation
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9]([NH2:12])[CH2:10][CH3:11])=[CH:5][C:4]=1[F:13].C(Cl)Cl.C1N=CN([C:22](N2C=NC=C2)=[O:23])C=1.Cl.[N:30]1[C:35]2[CH2:36][NH:37][CH2:38][CH2:39][C:34]=2[CH:33]=[N:32][C:31]=1[NH:40][C@@H:41]([CH2:44][CH3:45])[CH2:42][OH:43]>O>[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9]([NH:12][C:22]([N:37]2[CH2:38][CH2:39][C:34]3[CH:33]=[N:32][C:31]([NH:40][C@@H:41]([CH2:44][CH3:45])[CH2:42][OH:43])=[N:30][C:35]=3[CH2:36]2)=[O:23])[CH2:10][CH3:11])=[CH:5][C:4]=1[F:13]

Participants

6

Reactant 4

HCID 6344Dichloromethane2×HCID 682631,1'-CarbonyldiimidazoleHCID 68294121(S)-2-(5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-ylamino)butan-1-ol hydrochlorideHCID 86705486HCID 86705486, compound

Product 1

HCID 60199018N-((R)-1-(4-chloro-3-fluorophenyl)propyl)-2-((S)-1-hydroxybutan-2-ylamino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxamide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of 139 (0.173 g, 0.773 mmol) and DCM (5 mL) at RT was added TEA (0.235 g, 2.32 mmol) and CDI (0.125 g, 0.773 mmol) and the reaction was stirred at RT for 30 min. To this solution was added dropwise a solution of 216 (0.200 g, 0.773 mmol), TEA (0.235 g, 2.32 mmol) and DCM (5 mL) and the resulting solution stirred for 4 h then poured into water and extracted with DCM. The combined organic fractions were dried (MgSO4), filtered, and concentrated in vacuo. The crude product was purified by SiO2 chromatography eluting with DCM/MeOH (500:40) to afford 0.050 g (14.8%) of I-57: MS m/z (APCI-pos) M+1=436.

Workup

  1. stirringthe resulting solution stirred for 4 h
  2. extractionextracted with DCM
  3. dry with materialThe combined organic fractions were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by SiO2 chromatography
  7. washeluting with DCM/MeOH (500:40)
  8. customto afford 0.050 g (14.8%) of I-57: MS m/z (APCI-pos) M+1=436

Sources & evidence

ORD record
ord-18404f1cbf124719a3ad580854ec1c55
Source dataset
uspto-grants-2015_09
Patent number
US09133187B2

Reaction notes

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