Diisopropylethylamine → 2-({2-[(isoquinoline-3-carbonyl)-amino]-3H-benzoimidazole-4-carbonyl}-amino)-6,7-dihydro-4H-thiazolo[5,4-c]pyridine-5-carboxylic acid tert-butyl ester

HRID 1844985Notes

Reaction equation

HRID 1844985 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([C:11]([NH:13][C:14]2[NH:15][C:16]3[C:22]([C:23](O)=[O:24])=[CH:21][CH:20]=[CH:19][C:17]=3[N:18]=2)=[O:12])[N:2]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[C:59]([O:63][C:64]([N:66]1[CH2:71][CH2:70][C:69]2[N:72]=[C:73]([NH2:75])[S:74][C:68]=2[CH2:67]1)=[O:65])([CH3:62])([CH3:61])[CH3:60]>CN(C=O)C>[C:59]([O:63][C:64]([N:66]1[CH2:71][CH2:70][C:69]2[N:72]=[C:73]([NH:75][C:23]([C:22]3[C:16]4[NH:15][C:14]([NH:13][C:11]([C:3]5[N:2]=[CH:1][C:10]6[C:5]([CH:4]=5)=[CH:6][CH:7]=[CH:8][CH:9]=6)=[O:12])=[N:18][C:17]=4[CH:19]=[CH:20][CH:21]=3)=[O:24])[S:74][C:68]=2[CH2:67]1)=[O:65])([CH3:62])([CH3:60])[CH3:61]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11357283tert-butyl 2-amino-4H,5H,6H,7H-[1,3]thiazolo[5,4-c]pyridine-5-carboxylateHCID 178522491HCID 178522491, compound

Product 1

HCID 1784516582-({2-[(isoquinoline-3-carbonyl)-amino]-3H-benzoimidazole-4-carbonyl}-amino)-6,7-dihydro-4H-thiazolo[5,4-c]pyridine-5-carboxylic acid tert-butyl esterYield 55%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 0.25 g (0.75 mmol) of 2-[(isoquinoline-3-carbonyl)-amino]-3H-benzoimidazole-4-carboxylic acid in DMF (4 mL) was added 0.4 g (1.05 mmol) of HBTU and DIEA (1 mL). The mixture was stirred for 5 min and then 0.18 g (0.7 mmol) of 2-amino-6,7-dihydro-4H-thiazolo[5,4-c]pyridine-5-carboxylic acid tert-butyl ester was added. The resulting reaction mixture was heated at 80° C. for 2 h. After usual workup, the residue was purified by column chromatography to afford the 0.2 g (55%) of 2-({2-[(isoquinoline-3-carbonyl)-amino]-3H-benzoimidazole-4-carbonyl}-amino)-6,7-dihydro-4H-thiazolo[5,4-c]pyridine-5-carboxylic acid tert-butyl ester. LCMS: 570 (M+1)+. 1H NMR (DMSO-d6, 400 MHz): δ 9.56 (s, 1H), 8.84 (s, 1H), 8.35 (m, 2H), 7.96 (m, 4H), 7.84 (d, 1H), 7.35 (t, 1H), 4.58 (bs, 2H), 3.70 (t, 2H), 2.73 (t, 2H), 1.44 (s, 9H) ppm.

Workup

  1. customThe resulting reaction mixture
  2. customAfter usual workup, the residue was purified by column chromatography

Sources & evidence

ORD record
ord-803df39201714356afe3dd15e678550d
Source dataset
uspto-grants-2015_02
Patent number
US08946259B2

Reaction notes

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