3-(Tert-butyldimethylsilyloxy)-1-(3,4-difluorophenyl)propan-1-amine → N-(3-(tert-butyldimethylsilyloxy)-1-(3,4-difluorophenyl)propyl)-2-(isopropylamino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxamide

HRID 2279543Notes

Reaction equation

HRID 2279543 reaction equation
[Si:1]([O:8][CH2:9][CH2:10][CH:11]([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[C:15]([F:20])[CH:14]=1)[NH2:12])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].O1C[CH2:25][CH:24]([NH:27][C:28]2[N:29]=[CH:30][C:31]3[CH2:37][CH2:36][NH:35][CH2:34][C:32]=3[N:33]=2)[CH2:23]C1.Cl.ClC1C=C(C(C2[O:53][CH:52]=NC=2)N)C=CC=1Cl>>[Si:1]([O:8][CH2:9][CH2:10][CH:11]([NH:12][C:52]([N:35]1[CH2:36][CH2:37][C:31]2[CH:30]=[N:29][C:28]([NH:27][CH:24]([CH3:23])[CH3:25])=[N:33][C:32]=2[CH2:34]1)=[O:53])[C:13]1[CH:18]=[CH:17][C:16]([F:19])=[C:15]([F:20])[CH:14]=1)([C:4]([CH3:6])([CH3:7])[CH3:5])([CH3:3])[CH3:2]

Participants

4

Reactant 3

HCID 682943123-(Tert-butyldimethylsilyloxy)-1-(3,4-difluorophenyl)propan-1-amineHCID 68294638(3,4-Dichlorophenyl)(oxazol-5-yl)methanamine hydrochlorideHCID 71743546N-(tetrahydro-2H-pyran-4-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-amine

Product 1

HCID 131733487N-(3-(tert-butyldimethylsilyloxy)-1-(3,4-difluorophenyl)propyl)-2-(isopropylamino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxamideYield 31.9%

Procedure

Condensation of 306 and 72 was carried out in accord with the procedure described in step 6 of example 1 except 72 was used in place of 28 and 306 was used in place of 22. The crude product was purified by SiO2 chromatography eluting with a DCM/MeOH gradient (500:5 to 500:8) to afford 0.11 g (31.9%) of N-(3-(tert-butyldimethylsilyloxy)-1-(3,4-difluorophenyl)propyl)-2-(isopropylamino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxamide (308). The silyl group was removed with TBAF in accord with the procedure described in step 5 of example 42. The product was purified by SiO2 chromatography eluting with a DCM/MeOH gradient (500:15-500:25) to afford 0.010 g (12.8%) of I-77: MS m/z (APCI-pos) M+1=406.

Workup

  1. customThe crude product was purified by SiO2 chromatography
  2. washeluting with a DCM/MeOH gradient (500:5 to 500:8)

Sources & evidence

ORD record
ord-e6a9ab69a7e44f2a823188db43ebadb6
Source dataset
uspto-grants-2015_09
Patent number
US09133187B2

Reaction notes

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