HCID 57522618, compound → (1S,2S,3R,4R)-3-[5-chloro-2-(4-cyclopropylmethyl-7-methoxy-2-oxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-8-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide
Reaction equation
[NH2:1][C:2]1[C:3]([O:18][CH3:19])=[CH:4][C:5]2[CH2:11][N:10]([CH2:12][CH:13]3[CH2:15][CH2:14]3)[CH2:9][C:8](=[O:16])[NH:7][C:6]=2[CH:17]=1.Cl[C:21]1[N:26]=[C:25]([NH:27][C@@H:28]2[C@@H:33]3[CH2:34][C@@H:30]([CH:31]=[CH:32]3)[C@@H:29]2[C:35]([NH2:37])=[O:36])[C:24]([Cl:38])=[CH:23][N:22]=1>>[Cl:38][C:24]1[C:25]([NH:27][C@@H:28]2[C@@H:33]3[CH2:34][C@@H:30]([CH:31]=[CH:32]3)[C@@H:29]2[C:35]([NH2:37])=[O:36])=[N:26][C:21]([NH:1][C:2]2[C:3]([O:18][CH3:19])=[CH:4][C:5]3[CH2:11][N:10]([CH2:12][CH:13]4[CH2:14][CH2:15]4)[CH2:9][C:8](=[O:16])[NH:7][C:6]=3[CH:17]=2)=[N:22][CH:23]=1Participants
Reactant 2
Product 1
Procedure
In an analogous manner to procedure 1656g, 8-amino-4-cyclopropylmethyl-7-methoxy-1,3,4,5-tetrahydro-benzo[e][1,4]diazepin-2-one (150 mg, 0.57 mmol) and (1S,2S,3R,4R)-3-(2,5-dichloro-pyrimidin-4-ylamino)-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide (143 mg, 0.48 mmol) were coupled to afford (1S,2S,3R,4R)-3-[5-chloro-2-(4-cyclopropylmethyl-7-methoxy-2-oxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-8-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide (60 mg, 24%) as a mustard yellow solid following preparative tlc on silica gel (10% MeOH-DCM); 1H NMR (400 MHz, CDCl3) δ 8.28 (s, 2H), 7.90 (s, 1H), 7.52 (s, 1H), 7.16 (d, J=8 Hz, 1H), 6.79 (s, 1H), 6.30 (m, 3H), 5.69 (s, 1H), 4.38 (t, J=8 Hz, 1H), 3.93 (s, 3H), 3.78 (m, 2H), 3.43 (m, 2H), 3.06 (s, 1H), 2.87 (s, 1H), 2.57 (m, 3H), 2.24 (d, J=9 Hz, 1H), 1.60 (d, J=9 Hz, 1H), 0.92 (m, 1H), 0.59 (m, 2H), 0.22 (m, 2H); MS (m/e) 524 (M+1); mp 152° C.
Sources & evidence
- ORD record
- ord-e8c5dfddd8ad4113bb4309dd17b6449c
- Source dataset
- uspto-grants-2013_10
- Patent number
- US08552186B2
Reaction notes
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